Ca2+-activated K+ currents in rat locus coeruleus neurons induced by experimental ischemia, anoxia, and hypoglycemia.
ABSTRACT Ca2+-activated K+ currents in rat locus coeruleus neurons induced by experimental ischemia, anoxia, and hypoglycemia. J. Neurophysiol. 78: 2674-2681, 1997. The effects of metabolic inhibition on membrane currents and N-methyl--aspartic acid (NMDA)-induced currents were investigated in dissociated rat locus coeruleus (LC) neurons by using the nystatin perforated patch recording mode under voltage-clamp conditions. Changes in the intracellular Ca2+ concentration ([Ca2+]i) during the metabolic inhibition were also investigated by using the microfluometry with a fluorescent probe, Indo-1. Removal of both the oxygen and glucose (experimental ischemia), deprivation of glucose (hypoglycemia), and a blockade of electron transport by sodium cyanide (NaCN) or a reduction of the mitochondrial membrane potential with carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazone(FCCP) as experimental anoxia all induced a slowly developing outward current (IOUT) at a holding potential of -40 mV. The application of 10(-4) M NMDA induced a rapid transient peak and a successive steady state inward current and a transient outward current immediately after washout. All treatments related to metabolic inhibition increased the NMDA-induced outward current(INMDA-OUT) and prolonged the one-half recovery time of INMDA-OUT. The reversal potentials of both IOUT and INMDA-OUT were close to the K+ equilibrium potential (EK) of -82 mV. Either charybdotoxin or tolbutamide inhibited the IOUT and INMDA-OUT, suggesting the contribution of Ca2+-activated and ATP-sensitive K+ channels, even though the inhibitory effect of tolbutamide gradually diminished with time. Under the metabolic inhibition, the basal level of [Ca2+]i was increased and the one-half recovery time of the NMDA-induced increase in [Ca2+]i was prolonged. The IOUT induced by NaCN was inhibited by a continuous treatment of thapsigargin but not by ryanodine, indicating the involvement of inositol 1,4, 5-trisphosphate (IP3)-induced Ca2+ release (IICR) store. These findings suggest that energy deficiency causes Ca2+ release from the IICR store and activates continuous Ca2+-activated K+ channels and transient ATP-sensitive K+ channels in acutely dissociated rat LC neurons.
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- "All rights reserved. doi:10.1016/j.neuroscience.2010.06.028 1993; Murai et al., 1997; Stocker and Pedarzani, 2000; Torrecilla et al., 2002; Murai and Akaike, 2005 "
ABSTRACT: We have characterized the currents that flow during the interspike interval in mouse locus coeruleus (LC) neurons, by application of depolarizing ramps and pulses, and compared our results with information available for rats. A tetrodotoxin (TTX)-sensitive current was the only inward conductance active during the interspike interval; no TTX-insensitive Na(+) or oscillatory currents were detected. Ca(2+)-free and Ba(2+)-containing solutions failed to demonstrate a Ca(2+) current during the interspike interval, although a Ca(2+) current was activated at membrane potentials positive to -40 mV. A high- tetraethylammonium chloride (TEA) (15 mM) sensitive current accounted for almost all the K(+) conductance during the interspike interval. Ca(2+)-activated K(+), inward rectifier and low-TEA (10 muM) sensitive currents were not detected within the interspike interval. Comparison of these findings to those reported for neonatal rat LC neurons indicates that the pacemaker currents are similar, but not identical, in the two species with mice lacking a persistent Ca(2+) current during the interspike interval. The net pacemaking current determined by differentiating the interspike interval from averaged action potential recordings closely matched the net ramp-induced currents obtained either under voltage clamp or after reconstructing this current from pharmacologically isolated currents. In summary, our results suggest the interspike interval pacemaker mechanism in mouse LC neurons involves a combination of a TTX-sensitive Na(+) current and a high TEA-sensitive K(+) current. In contrast with rats, a persistent Ca(2+) current is not involved.Neuroscience 09/2010; 170(1):166-77. DOI:10.1016/j.neuroscience.2010.06.028 · 3.33 Impact Factor
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- "We have been also interested in studying how DAcontaining neurons react to another form of metabolic stress, represented by hypoglycemia, a condition in which glucose, the major substrate for neuronal energy production, is omitted from extracellular medium (ACSF). It is well known that hypoglycemia inhibits neuronal activity in different areas of the central nervous system, including hypothalamus, hippocampus, locus coeruleus and striatal aspiny neurons (Ashford et al., 1990; Tromba et al., 1992; Izumi et al., 1994; Calabresi et al., 1997; Murai et al., 1997; Rabinovici et al., 2000). We found that also DA-containing neurons of the midbrain become silent when perfused by glucose-free ACSF (Marinelli et al., 2000): their tonic firing discharge is abolished and the membrane potential hyperpolarizes (Fig. 8A). "
ABSTRACT: Metabolic stress associated to mitochondrial dysfunction has been put forward as an important factor causing degeneration of mesencephalic dopamine-containing neurons in Parkinson's disease (PD). Here we overview how these neurons react to acute hypoxia or hypoglycemia, that are conditions of energy deprivation causing a reduced production of ATP by mitochondria. These neurons, which show a tonic firing discharge under normal condition, undergo into membrane hyperpolarization during hypoxia or hypoglycemia that silence their spontaneous activity. We outline the cellular mechanisms causing membrane hyperpolarization and the accompanied disturbances of intracellular calcium and sodium homeostasis. A better understanding of the changes occurring during transient energy deprivation might contribute to understand the physiopathology of these neurons that derives from mitochondrial dysfunction.NeuroToxicology 11/2005; 26(5):857-68. DOI:10.1016/j.neuro.2005.01.013 · 3.05 Impact Factor
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- "In our study, the response of increased BK Ca activities after NaOCN introduction in H19-7 cells suggests that an initial calcium influx and then stimulate activities of BK Ca channels. The [Ca 2+ ] i mobilization contributes to outward currents by BK Ca during reduced oxygen tension is consistent with previous studies  . The increased activities of BK Ca channels in our study also suggest one of the possible mechanisms that lead to decreased neuronal excitability during a relatively mild form of chemical hypoxic state by NaOCN in neurons. "
ABSTRACT: We investigated the chemical toxic agent sodium cyanate (NaOCN) on the large conductance calcium-activated potassium channels (BK(Ca)) on hippocampal neuron-derived H19-7 cells. The whole-cell and cell-attach configuration of patch-clamp technique were applied to investigate the BK(Ca) currents in H19-7 cells in the presence of NaOCN (0.3 mM). NaOCN activated BK(Ca) channels on H19-7 cells. The single-channel conductance of BK(Ca) channels was 138+/-7pS. The presence of NaOCN (0.3 mM) caused an obvious increase in open probability of BK(Ca) channels. NaOCN did not exert effect on the slope of the activation curve and stimulated the activity of BK(Ca) channels in a voltage-dependent fashion in H19-7 cells. The presence of paxilline or EGTA significantly reduced the BK(Ca) amplitude, in comparison with the presence of NaOCN. These findings suggest that during NaOCN exposure, the activation of BK(Ca) channels in neurons could be one of the ionic mechanisms underlying the decreased neuronal excitability and neurological disorders.Neuroscience Letters 04/2005; 377(2):110-4. DOI:10.1016/j.neulet.2004.11.081 · 2.06 Impact Factor