I S Kiseleva

Humboldt-Universität zu Berlin, Berlín, Berlin, Germany

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Publications (24)53.09 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of NO in the regulation of currents passing through ion channels activated by cell stretching (mechanically gated channels, MGC), particularly through cation-selective K(+)-channels TRPC6, TREK1 (K(2P)2.1), and TREK2 (K(2P)10.1), was studied on isolated mouse, rat, and guinea pig cardiomyocytes using whole-cell patch-clamp technique. In non-deformed cells, binding of endogenous NO with PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxy-3-oxide) irreversibly shifted the diastolic membrane potential towards negative values, modulates K(ir)-channels by reducing I(K1), and blocks MGC. Perfusion of stretched cells with PTIO solution completely blocked MG-currents. NO-synthase inhibitors L-NAME and L-NMMA completely blocked MGC. Stretching of cardiomyocytes isolated from wild type mice and from NOS1(-/-)- and NOS2(-/-)- knockout mice led to the appearance in MG-currents typical for the specified magnitude of stretching, while stretching of cardiomyocytes from NOS3(-/-)- knockout mice did not produce in MG-current. These findings suggest that NO plays a role in the regulation of MGC activity and that endothelial NO-synthase predominates as NO source in cardiomyocyte response to stretching.
    Bulletin of Experimental Biology and Medicine 12/2010; 150(2):263-7. · 0.34 Impact Factor
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    ABSTRACT: Whole-cell ionic currents through mechanically gated channels (MGC) were recorded in isolated cardiomyocytes under voltage clamp conditions. In unstrained cells, NO donors SNAP and DEA-NO activated MGC and induced MG-like currents. In contrast, in stretched cells with activated MGC, these NO-donors inactivated and inhibited MGC.
    Bulletin of Experimental Biology and Medicine 07/2010; 150(1):1-5. · 0.34 Impact Factor
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    A Kamkin, S Kirischuk, I Kiseleva
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    ABSTRACT: Mechanosensitive conductances were reported in cardiac fibroblasts, but the properties of single channels mediating their mechanosensitivity remain uncharacterized. The aim of this work was to investigate single mechano-gated channels (MGCs) activated by mechanical deformations of cardiac fibroblasts. Currents through single MGCs and mechanosensitive whole-cell currents were recorded from isolated rat atrial fibroblasts using the cell-attached and whole-cell patch-clamp configurations respectively. Defined mechanical stress was applied via the patch pipette used for the whole-cell recordings. Under resting conditions occasional short openings of two types of single MGCs with conductances of 43 and 87 pS were observed. Both types of channels displayed a linear current-voltage relationship with the reversal potential around 0 mV. Small (1 microm) mechanical deformations affected neither single nor whole-cell mechano-gated currents. Cell compressions (2, 3 and 4 microm) augmented the whole-cell currents and increased the frequency and duration of single channel openings. Cell stretches (2, 3 and 4 microm) inactivated the whole-cell currents and abolished the activity of single MGCs. Gd(3+) (8 microm) blocked the whole-cell currents within 5 min. No single channel activity was observed in the cell-attached mode when Gd(3+) was added to the intrapipette solution. Cytochalasin D and colchicine (100 microm each) completely blocked both the whole-cell and single channel currents. These findings show that rat atrial fibroblasts express two types of MGCs whose activity is governed by cell deformation. We conclude that fibroblasts can sense the direction of applied stress and contribute to mechano-electrical coupling in the heart.
    Acta Physiologica 07/2010; 199(3):277-92. · 4.38 Impact Factor
  • A Kamkin, I Kiseleva, I Lozinsky, H Scholz
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    ABSTRACT: Fibroblasts in the heart can respond to mechanical deformation of the plasma membrane with characteristic changes of their membrane potential. Membrane depolarization of the fibroblasts occurs during the myocardial contractions and is caused by an influx of cations, mainly of sodium ions, into the cells. Conversely, application of mechanical stretch to the cells, i.e., during diastolic relaxation of the myocardium, will hyperpolarize the membrane potential of the fibroblasts due to reduced sodium entry. Thus, cardiac fibroblasts can function as mechano-electric transducers that are possibly involved in the mechano-electric feedback mechanism of the heart. Mechano-electric feedback refers to the phenomenon, that the cardiac mechanical environment, which depends on the variable filling pressure of the ventricles, modulates the electrical function of the heart. Increased sensitivity of the cardiac fibroblasts to mechanical forces may contribute to the electrical instability and arrhythmic disposition of the heart after myocardial infarction. Novel findings indicate that these processes involve the intercellular transfer of electrical signals between fibroblasts and cardiomyocytes via gap junctions. In this article we will discuss the recent progress in the electrophysiology of cardiac fibroblasts. The main focus will be on the intercellular pathways through which fibroblasts and cardiomyocytes communicate with each other.
    Archiv für Kreislaufforschung 08/2005; 100(4):337-45. · 5.90 Impact Factor
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    ABSTRACT: When atrial tissue contracts, mechanically induced potentials (MIPs) are generated in fibroblasts, presumably by activation of a non-selective cation conductance Gns. Non-stimulated atrial fibroblasts had a mean (+/-SD) membrane potential (Em) of -22 +/- 2 mV and an input resistance of 510 +/- 10 MS. MIP amplitude (AMIP) was 38+/-4 mV when current injection had polarised Em to Vm = -50 mV. The slope of the function relating AMIP to Vm can be regarded as a mechanosensitive factor (Xms) that describes the relative increase in Gns during a MIP. Putative involvement of cytoskeletal fibres in activation of Gns was studied by delivering drugs from the intracellular recording microelectrode. Destabilisation of F-actin by 0.2 mM cytochalasin D reduced AMIP from 38 to 16 mV and Xms from 5 to 1.8. Destabilisation of tubulin with 0.2 mM colchicine reduced AMIP to 21 mV and Xms to 2.1. The combination colchicine plus cytochalasin D reduced AMIP to 9 mV and Xms to 1.4. Promoting F-actin stability with exogenous adenosine 5'-triphosphate (ATP) increased AMIP and Xms and attenuated the effects of cytochalasin D. Similarly, facilitation of tubulin stability with guanosine 5'-triphosphate (GTP) or taxol increased AMIP and Xms and attenuated the effects of colchicine. The results suggest that transfer of mechanical energy from the deformed fibroblast surface to the Gns channel protein depends on intact F-actin and tubulin fibres.
    Pflügers Archiv - European Journal of Physiology 08/2001; 442(4):487-97. · 4.87 Impact Factor
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    ABSTRACT: 1. The functional consequences of a lack of endothelial nitric oxide synthase (eNOS) on left ventricular force development and the anti-adrenergic effect of acetylcholine (ACh) were investigated in isolated hearts and cardiomyocytes from wild type (WT) and eNOS knockout (eNOS-/-) mice. 2.eNOS expression in cardiac myocytes accounted for 20 % of total cardiac eNOS (Western blot analysis). These results were confirmed by RT-PCR analysis. 3. In the unstimulated perfused heart, the left ventricular pressure (LVP) and maximal rate of left ventricular force development (dP/dtmax) of eNOS-/- hearts were not significantly different from those of WT hearts (LVP: 97 +/- 11 mmHg WT vs. 111 +/- 11 mmHg eNOS-/-; dP/dtmax: 3700 +/- 712 mmHg s(-1) WT vs. 4493 +/- 320 mmHg s)-1) eNOS-/-). 4. The dobutamine (10-300 nM)-induced increase in LVP was enhanced in eNOS-/- hearts. In contrast, L-type Ca2+ currents (ICa,L) in isolated cardiomyocytes of WT and eNOS-/- hearts showed no differences after beta-adrenergic stimulation. Dibutyryl-cGMP (50 microM) reduced basal ICa,L in WT cells to 72 +/- 12 % while eNOS-/- ICa,L was insensitive to the drug. The pre-stimulated ICa,L (30 nM isoproterenol) was attenuated by dibutyryl-cGMP in WT and eNOS-/- cells to the same extent. 5. The Ca2+ (1.5-4.5 mM)-induced increase in inotropy was not different between the two experimental groups and beta-adrenergic receptor density was increased by 50% in eNOS-/- hearts. 6. The contractile effects of dobutamine could be inhibited almost completely by ACh or adenosine. The extent of the anti-adrenergic effect of both compounds was identical in WT and eNOS-/- hearts. Measurement of ICa,L in isolated cardiac myocytes yielded similar results. 7. These data demonstrate that in the adult mouse (1) lack of eNOS is associated with increased cardiac contractile force in response to beta-adrenergic stimulation and with elevated -adrenergic receptor density, (2) the unaltered response of ICa,L in eNOS-/- cardiac myocytes to beta-adrenergic stimulation suggests that endothelium-derived NO is important in mediating the whole-organ effects and (3) eNOS is unimportant for the anti-adrenergic effect of ACh and adenosine.
    The Journal of Physiology 05/2001; 532(Pt 1):195-204. · 4.38 Impact Factor
  • A G Kamkin, I S Kiseleva, V N Iarygin
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    ABSTRACT: This article is dedicated to the mechanism of mechano-electric feedback in heart. The evidence is briefly discussed on organ, tissue, cell and in details on cell membrane levels in case of application of one of applied mechanical stimulus to cardiomyocytes. Stretch of the hole heart or its tissue fragment causes quick starting repolarization of action potentials (AP)/monophasic action potentials (MAP), shift of AP/MAP plato to higher negative zone, appearance of peaks of stretch-induced depolarization (SID) on final phase of AP/MAP repolarization level, which are overgrowing into extra AP/extra MAP. Mechanical events (changes in length and force of contractions) change electrical processes by means of direct influence on cell membrane via stretch activated channels (SAC). Cardiomyocytes, isolated from animal atrium and animal and human ventricular are responsible for the stretch of depolarized membrane, prolongation of AP and appearance of extra AP (extra systoles). Analysis of experiments, conducted following the patch clamp method in whole cell configuration, shows that the main cause of that mechanical events is SAC current--ISAC. During negative potential ISAC is determined by incoming into the cell sodium ions and is negative. Negative ISAC is changing final phase of AP/MAP repolarization and causes SID, which is overgrowing into extra AP (extra systoles), in case that SID exceeds threshold. Fast AP repolarization and AP plato shift into higher negative zone is related to positive ISAC (living potassium ions through SAC), activation of IK and reduction of ISAC. Activation of ISAC and arrhythmia induction require lower mechanical stimulus for hypertrophied cardiomyocytes, in comparisment to healthy ones. Hypertrophy of cardiomyocytes can lead to expression of SAC therefore increasing channel density and ISAC maximum amplitude. In this article is discussing data, acquired by means of direct measurement of conduction of single SAC on the background of mechanical stimulation of the cardiomyocytes membrane. It contains characteristics of the estimated SACs. It is shown that blocking of conduction of ions through SAC prevents mechanically induced arrhythmia in healthy and hypertrophied cardiomyocytes, which transforms the problem of mechano-electric feedback in heart from purely fundamental into clinical one.
    Uspekhi fiziologicheskikh nauk 01/2001; 32(2):58-87.
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    A Kamkin, I Kiseleva, G Isenberg
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    ABSTRACT: Mechanical dilation of the human ventricle is known to induce arrhythmias, the underlying ionic mechanisms, however, remain to be clarified. Ventricular myocytes isolated from human, guinea-pig or rat hearts were stretched between the patch electrode and a glass stylus. Local stretch prolonged the action potential, depolarized the resting membrane and caused extra systoles. Under voltage-clamp conditions, stretch activated several ionic current components. The most prominent current was a stretch activated current (I(SAC)) through non-selective cation channels. I(SAC) followed a linear voltage-dependence, reversed polarity close to 0 mV and was suppressed by 5 microM Gd(3+). During stretch, I(SAC) became steady within 200 ms. I(SAC) did not inactivate and it completely disappeared upon relaxation. Stretch-sensitivity was evaluated from the slope of I(SAC) versus amplitude of stretch. Stretch sensitivity was 75 pA/microm in myocytes from young (3 month), 143 pA/microm in myocytes from old (15 months), and 306 pA/microm in hypertrophied myocytes from old (15 months) spontaneously hypertensive animals. Stretch sensitivity was 262 pA/microm in hypertrophied myocytes from human failing hearts, and it was 143 pA/microm in guinea-pig ventricular myocytes. Local stretch of adult single ventricular myocytes can induce arrhythmias that resemble surface-recordings from whole hearts. Stretch modulates multiple current components, I(SAC) being the current with the largest arrhythmogenic potential. Stretch-sensitivity of I(SAC) is higher in hypertrophied than in control myocytes as can be expected from the observation that hypertrophy and failure increase the risk of stretch-induced arrhythmias.
    Cardiovascular Research 01/2001; 48(3):409-20. · 5.81 Impact Factor
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    ABSTRACT: Left ventricular myocardial infarction (MI) can lead to alterations in hemodynamic load conditions, thereby inducing right atrial hypertrophy and dilatation associated with phenotypic modulation of cardiomyocytes, electrical abnormalities, rhythm disturbances, and atrial fibrillation. However, there is limited information on the electrophysiological basis for these events. We investigated whether atrial stretch in the setting of chronic MI modulates the electrophysiological properties of cardiomyocytes via "mechano-electric feedback", providing a mechanism for atrial arrhythmia after ventricular infarction. Five weeks after left ventricular MI (n=37), action potentials (AP) were measured in right atrial tissue preparations using a current clamp scheme, and compared to sham-operated rats (SO, n=10). Contractile activity was recorded at a preload of 1 mN, and sustained stretch was applied via a micrometer. In SO, stretch of 1.75 mN shortened repolarization at 50% and prolonged it at 90%. In MI, mechanically-induced electrical alterations were observed at a significantly lower level of stretch than in SO (0.19 mN). Sustained stretch in MI prolonged AP at 90% repolarization giving rise to stretch-activated depolarizations (SAD) near 90% repolarization (SAD90). When reaching threshold for premature APs, electrical phenomena similar to atrial fibrillations were seen in some preparations. Moreover, we observed APs with prolonged duration at 25%, 50%, and 90% repolarization where stretch induced SAD near 50%. Gadolinium used at a concentration to inhibit stretch-activated channels (40microM) suppressed mechanically-induced electrical events. In conclusion, increased susceptibility after MI to mechanical stretch may predispose atrial cardiomyocytes to arrhythmia. These mechano-electrical alterations are sensitive to gadolinium suggesting involvement of stretch-activated ion channels.
    Journal of Molecular and Cellular Cardiology 04/2000; 32(3):465-77. · 5.15 Impact Factor
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    ABSTRACT: The effects of chronic treatment with the beta-adrenoceptor antagonist metoprolol, the angiotensin converting enzyme inhibitor ramipril, their combination, or placebo on action potential configuration 6 weeks after myocardial infarction in rats were studied. Action potentials were measured in isolated left ventricular posterior papillary muscles and compared with action potentials from a sham operated group without infarction. After infarction, the action potential amplitude was reduced and this phenomenon was partially reversed by metoprolol- and ramipril-treatment. Prolonged repolarisation after infarction compared to sham operated animals was additionally delayed after metoprolol treatment. Thus, metoprolol extends the refractory period, which may counteract tachyarrhythmia.
    European Journal of Pharmacology 03/2000; 388(3):263-6. · 2.59 Impact Factor
  • A G Kamkin, I S Kiseleva
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    ABSTRACT: The article discusses the issues of possible connection between mechanical phenomena in myocardium and the electrical processes. Not only cardiomyocytes, but also cardiac fibroplastic are considered as substratum for the mechanisms of mechano-electrical feedbacks. Cardiomyocytes and fibroplastic of healthy animals demonstrate the mechano-electrical feedbacks, which essentially mean that stretching of the cardiac tissue within the physiological limits to 2 mN changes the electrophysiological cell processes. Close to 90% repolarization potential of cardiomyocytes action the mechano-induced depolarization develops; over the background of depolarization, when it reaches the threshold values, extra potentials of action are generated. In fibroplastic, membrane mechano-induced hyperpolarization develops; as result of cellular interaction it may develop hyperpolarization of pacemaking cells of the right auricle and slow the cardiac rythm down. In case of a pathology, for instance, infarct of the left heart ventricle modification of electric cell activity was detected at quite low values of tissue stretching up to 0.2. mN. Mechano-induced depolarization of cardiomyocytes of animals affected by infarct develops at 50% level of repolarization phase of action potential, or at 90% of repolarization phase. In the former case development of mechano-induced depolarization coincides with the period of absolute cell refractering. Extra action potential develops immediately after the refractering phase when the mechano-induced depolarization shifts the membrane potential towards threshold values. In the latter case the mechano-induced depolarization transforms into extra action potential. With further stretching fibrillation develops. In fibroplastic the values of mechano-induced membrane hyperpolarization grow with greater scope of infarct damage. Magnitude of mechano-induced hyperpolarization of auricle fibroplastic taken from the animals with infarcts shows dependence on the period of remodelling if stretching is tissue is a standard parameter. With prolongation of the remodelling period the value of mechano-induced fibroplastic hyperpolarization diminishes. The problem of developing the combinations eliminating mechano-induced cardiac arrhythmia is raised.
    Uspekhi fiziologicheskikh nauk 01/2000; 31(2):51-78.
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    ABSTRACT: It has been shown that cardiac fibroblasts of the human heart are electrically non-excitable and mechanosensitive. The resting membrane potential of these cells is -15.9+/-2.1 mV and the membrane resistance is 4.1+/-0.1 G[Omega]. Rhythmic contractions of the myocardium associated with stretch of the surrounding tissue produce reversible changes in the membrane potential of cardiac fibroblasts. These mechanically induced potentials (MIPs) follow the rhythm of myocardial contractions. Simultaneous recording of the action potential of cardiomyocytes and MIPs of cardiac fibroblasts demonstrates a delay of 40.0+/-0.4 ms after the action potential before the appearance of the MIP. Contraction produces a MIP which is more positive or more negative than the reversal potential - the membrane potential due to current injection at which the MIP reverses its direction. Regardless of the initial orientation of the MIP, intracellular polarization increases the amplitude towards the reversal potential if the background MIP had depolarized the membrane or away from the reversal potential if the initial background MIP had hyperpolarized the membrane. Artificial intracellular polarization changed the amplitude but not the frequency of the MIP. The pool of electrically non-excitable mechanosensitive cells, which change their electrical activity during contraction and relaxation of the heart, may play a role in the mechano-electrical feedback mechanism which has to be taken into account in the normal function of the heart as well as in pathological processes.
    Experimental Physiology 04/1999; 84(2):347-56. · 2.79 Impact Factor
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    ABSTRACT: Electrically non-excitable but mechanosensitive right-atrial fibroblasts are thought to be involved in the chronotropic response of the heart to stretch. After myocardial infarction, altered chronotropic response may be due to the remodeling process which also involves the right atrium. Remodeling is associated with the development of hypertrophy of cardiomyocytes and proliferation of fibroblasts. Electrical properties of atrial mechanosensitive fibroblasts from chronic infarcted hearts and their possible role for altered chronotropic response has not, to our knowledge, been studied until now. Thus, resting membrane potential as well as mechanically induced potential of fibroblasts, action potential (AP) of cardiomyocytes, spontaneous frequency and mechanical activity of preparations from the sinus node region were studied 10 weeks after myocardial infarction induced by ligation of the left coronary artery in rats. The prolongation of AP repolarization (increases in APD50 and APD90) correlated closely to the infarct size (IS) and the degree of hypertrophy, respectively. Along with increasing IS, membrane potentials of fibroblasts were shifted to more negative values, with a peak of frequency distribution at -15 mV (control and very small IS), at -35 mV (intermediate IS), and -55 mV (large IS), and spontaneous electrical activity was decreased. Membrane resistance of fibroblasts also correlated to IS and was eight-fold greater at large IS than in control. We hypothesize that, in the infarcted heart, increased membrane potential and membrane resistance of fibroblasts may alter electrical activity of neighbouring myocytes in the sinus-venosus region via intercellular electrical coupling.
    Journal of Molecular and Cellular Cardiology 07/1998; 30(6):1083-93. · 5.15 Impact Factor
  • A G Kamkin, I S Kiseleva
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    ABSTRACT: Electrically non-excitable fibroblasts, which represent the other population of cells abundant in the sino-atrial node region, have been reported to be mechanosensitive in the frog and in the rat heart. It was shown that these cells respond to artificial or contraction-induced stretch of the atrial wall by a change in membrane potential. These changes could be explained by the operation of stretch-activated channels and intracellular calcium oscillation. Influences of cardiac fibroblasts on electrophysiological properties of cardiomyocytes would require interaction between these cells. In tissue culture studies, it has been shown, that fibroblasts and cardiomyocytes form nexus connections. In recent studies on fibroblast-cardiomyocyte junctions in the rabbit heart pacemaker region, non nexus-like contacts clearly dominated. These membrane non nexus-like contacts might promote capacitive interactions between heterologous cells, which has been demonstrated independently in electrophysiological studies. Through these contacts, the fibroblast membrane potential may affect the membrane potential of neighbouring myocytes in the right atrium which may play an important role for the chronotropic response of the heart to mechanical stretch of the right atrial wall. Electrically non-excitable but mechanosensitive cardiac fibroblasts can act as a substrate for an intracardiac mechano-electrical feedback mechanism by which mechanical changes, e.g. stretch, modulate the electrical activity. In the atria, fibroblasts may act as volume and mechanical sensors, respectively.
    Uspekhi fiziologicheskikh nauk 01/1998; 29(1):72-102.
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    I Kiseleva, A Kamkin, P Kohl, M J Lab
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    ABSTRACT: Electrically non-excitable cardiac fibroblasts in the sino-atrial node region are mechano-sensitive. Rhythmic contraction of adjacent myocardium, or artificial stretch of the tissue, produce a reversible change in the membrane potential: mechanically induced potentials (MIP). Stretch of normal cardiomyocytes can be associated with intracellular calcium changes. The purpose of this study is to use pharmacological interventions to investigate the possibility that stretch-induced Ca2+ entry through ion channels in the sarcolemma and Ca2+ release from internal stores play a role in MIP generation. Isolated spontaneously contracting or artificially stretched preparations of right atrium of rat heart were superfused with physiological solutions. An intracellular floating microelectrode recorded fibroblast MIPs and was also used for injection of current. A dye, Lucifer yellow, applied through the micropipette, identified recording sites. We assessed the role of extracellular Ca2+ using EGTA in the bathing solution. For the role of intracellular Ca2+ in the generation of MIP, several substances that influence [Ca2+]i handling were applied intracellularly by diffusion from the recording microelectrode. These include: BAPTA (to chelate intracellular Ca2+); BHQ, thapsigargin and CPA (to deplete Ca2+ from intracellular stores by inhibition of the endoplasmic reticulum (ER) ATP Ca2+ pump), and caffeine and ryanodine (to induce ER Ca2+ release). All the pharmacological compounds which were introduced intracellulary, and EGTA applied extracellularly, decreased the amplitude of the MIP to variable degrees. Only thapsigargin induced a bi-phasic response with an initial increase in MIP amplitude, followed by a decrease. MIP duration was reduced by most interventions, exceptions being low extracellular Ca2+, BHQ and ryanodine. Short duration extracellular application of caffeine, which was added to the perfusate as a secondary contractile stimulus, partly restored the MIPs by activation of cardiac contraction. Intracellular current injection, before any intervention, linearly altered both membrane potential (Em) and MIP amplitude (Vm). Application of compounds listed above introduced non-linearity to the Em/Vm relationship. We suggest that mechanically induced Ca2+ influx, induced through stretch-activated channels in the plasma membrane, and release of Ca2+ from the endoplasmic reticulum, play key roles in the mechanism of MIP generation. Further, our results demonstrate the existence of functional ryanodine/caffeine-sensitive Ca2+ stores in cardiac fibroblasts.
    Cardiovascular Research 08/1996; 32(1):98-111. · 5.81 Impact Factor
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    P Kohl, A G Kamkin, I S Kiseleva, D Noble
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    ABSTRACT: The positive chronotropic response of the heart to stretch of the right atrium is one of the major mechanisms adjusting the heart rate to variations in venous return on a beat-by-beat basis. The precise pathway of this mechano-electric feedback and its cellular basis are uncertain. In this study, a possible contribution of mechanosensitive fibroblasts, abundant in the sino-atrial node region, was investigated using a mathematical model of the electrical interaction of a mechanosensitive fibroblast and a sino-atrial pacemaker cell. Electrophysiological evidence for a bio-electrical interaction of mechanosensitive fibroblasts with surrounding cardiomyocytes has been studied in (i) the isolated spontaneously beating atrium of rat hearts, and (ii) cell cultures of the neonatal rat heart. These investigations were performed using (i) double-barrelled floating microelectrodes for intracellular potential registrations, and (ii) the double whole cell patch-clamp technique. It was shown that cardiac fibroblasts and surrounding cardiomyocytes can be either electrically well isolated from each other, or coupled both capacitively and electrotonically. The electrophysiological data obtained were incorporated into the OXSOFT HEART program. Assuming that equivalent coupling may occur between mechanosensitive fibroblasts and sino-atrial pacemaker cells, a heterologous cell pair consisting of one fibroblast and one sino-atrial node myocyte connected by ten to thirty single gap junctional channels with a conductance of 30 pS was modelled. The model of the electrotonic interaction of these cells showed that stretch of the fibroblast during atrial diastole, simulating increased atrial wall tension during atrial filling, can raise the spontaneous depolarization rate of the pacemaker cell in a stretch-dependent manner by up to 24%. These results show that cardiac mechanosensitive fibroblasts could form a cellular basis for the positive chronotropic response of the heart to stretch of the right atrium.
    Experimental Physiology 12/1994; 79(6):943-56. · 2.79 Impact Factor
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    P Kohl, A G Kamkin, I S Kiseleva, T Streubel
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    ABSTRACT: Mechanosensitive cells were found in the sinus venosus and right atrium of the frog heart. Their intracellular membrane potentials were studied in spontaneously beating hearts and in artificially stretched preparations. Membrane resistance was indirectly proportional to the stretch applied. The electrophysiological data and distribution of these cells in the heart led to the conclusion that they are cardiac fibroblasts.
    Experimental Physiology 02/1992; 77(1):213-6. · 2.79 Impact Factor
  • Doklady Akademii nauk SSSR 02/1987; 292(6):1502-5.
  • A G Kamkin, I S Kiseleva, G I Kositskiĭ
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    ABSTRACT: The hypothesis of neuropeptides involvement in intercellular interaction was checked on the neurons VD1 and RPD2 connected with electrotonic synapse with two-way transmission in nerve ganglia of the pond snail. The preparation was perfused with natural and synthetic fragments of ACTH (2 X 10(-7) M). In perfusion with ACTH4-10 solution, synapse became rectified whereas in ACTH4-7 and ACTH5-10 solutions it obtained partially rectified properties. After exposure to ACTH4-7--Pro--Gly--Pro, synapse obtained rectifying properties with one--way increase in conductivity following temporary two-way increase of transmission efficiency. With the use of Pro--Gly--Pro--ACTH4-7--Pro--Gly--Pro, inhibition of the two--way conductivity occurred. Neuropeptides seem to modulate synaptic transmission. Impulse priority depends on the initial level of the cell MPs and is purposefully modulated by the peptides under test.
    Fiziologicheskiĭ zhurnal SSSR imeni I. M. Sechenova 08/1986; 72(7):908-20.
  • Doklady Akademii nauk SSSR 02/1986; 287(5):1266-9.