Changes in force and cytosolic Ca2+ concentration after length changes in isolated rat ventricular trabeculae.
ABSTRACT 1. Changes in cytosolic [Ca2+] ([Ca2+]i) were measured in isolated rat trabeculae that had been micro-injected with fura-2 salt, in order to investigate the mechanism by which twitch force changes following an alteration of muscle length. 2. A step increase in length of the muscle produced a rapid potentiation of twitch force but not of the Ca2+ transient. The rapid rise of force was unaffected by inhibiting the sarcoplasmic reticulum (SR) with ryanodine and cyclopiazonic acid. 3. The force-[Ca2+]i relationship of the myofibrils in situ, determined from twitches and tetanic contractions in SR-inhibited muscles, showed that the rapid rise of force was due primarily to an increase in myofibrillar Ca2+ sensitivity, with a contribution from an increase in the maximum force production of the myofibrils. 4. After stretch of the muscle there was a further, slow increase of twitch force which was due entirely to a slow increase of the Ca2+ transient, since there was no change in the myofibrillar force-[Ca2+]i relationship. SR inhibition slowed down, but did not alter the magnitude of, the slow force response. 5. During the slow rise of force there was no slow increase of diastolic [Ca2+]i, whether or not the SR was inhibited. The same was true in unstimulated muscles. 6. We conclude that the rapid increase in twitch force after muscle stretch is due to the length-dependent properties of the myofibrils. The slow force increase is not explained by length dependence of the myofibrils or the SR, or by a rise in diastolic [Ca2+]i. Evidence from tetani suggests the slow force responses result from increased Ca2+ loading of the cell during the action potential.
Article: Osmotic compression of single cardiac myocytes eliminates the reduction in Ca2+ sensitivity of tension at short sarcomere length.[show abstract] [hide abstract]
ABSTRACT: According to the Frank-Starling relation, cardiac output varies as a function of end-diastolic volume of the ventricle. The cellular basis of the relation is thought to involve length-dependent variations in Ca2+ sensitivity of tension; ie, as sarcomere length is increased in cardiac muscle, Ca2+ sensitivity of tension also increases. One possible explanation for this effect is that the decrease in myocyte diameter as muscle length is increased reduces the lateral spacing between thick and thin filaments, thereby increasing the likelihood of cross-bridge interaction with actin. To examine this idea, we measured the effects of osmotic compression of single skinned cardiac myocytes on Ca2+ sensitivity of tension. Single myocytes from rat enzymatically digested ventricles were attached to a force transducer and piezoelectric translator, and tension-pCa relations were subsequently characterized at short sarcomere length (SL), at the same short SL in the presence of 2.5% dextran, and at long SL. The pCa (-log[Ca2+]) for half-maximal tension (ie, pCa50) increased from 5.54 +/- 0.09 to 5.65 +/- 0.10 (n = 7, mean +/- SD, P < .001) as SL was increased from approximately 1.85 to approximately 2.25 microns. Osmotic compression of myocytes at short length also increased Ca2+ sensitivity of tension, shifting tension-pCa relations to [Ca2+] levels similar to those observed at long length (pCa50, 5.68 +/- 0.11). These results support the idea that the length dependence of Ca2+ sensitivity of tension in cardiac muscle arises in large part from the changes in interfilament lattice spacing that accompany changes in SL.Circulation Research 08/1995; 77(1):199-205. · 9.49 Impact Factor
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ABSTRACT: The aim of this study was to characterize the relationship of perfusate calcium concentration, contractile state and stability of the isolated crystalloid perfused working rat heart preparation, to ischemic duration and functional recovery, at a physiological perfusate calcium concentration. In the first protocol, hearts (n = 6 per group) were aerobically perfused for up to 300 mins with Krebs Henseleit solution containing calcium concentrations (total) of 1.0, 1.2, 1.4, 1.6, 1.8 and 2.5 mmol/L (equivalent to ionized concentrations of 0.76, 0.94, 1.15, 1.21, 1.58 and 2.25 mmol/L, respectively). After 120 mins, aortic flow decreased by less than 20% in all preparations except those perfused with 1.0 mmol/L, which fell by over 60%. For subsequent studies, a calcium concentration of 1.4 mmol/L (ionized calcium 1.15 mmol/L, a value equivalent to plasma ionized calcium) was identified as ideal and shown to be associated with stable function and adequate inotropic reserve. The second protocol was as follows: In additional studies (n = 6 per group), the relationship between normothermic global ischemic duration (with or without cardioplegic arrest) and post ischemic functional recovery was characterized. Increasing the ischemic duration (10, 15, 20, 25, 30, 35 or 40 mins) progressively impaired recovery of aortic flow to 86.7 +/- 3.2%, 71.7 +/- 4.9%, 27.7 +/- 5.0%, 14.5 +/- 12.3%, 0%, 0% and 0%, respectively, in the noncardioplegia group, and to 84.7 +/- 1.7%, 85.0 +/- 2.9%, 78.0 +/- 2.4%, 56.0 +/- 7.8%, 32.2 +/- 6.0%, 6.5 +/- 3.7% and 0%, respectively, in the cardioplegia group. These results were similar to those of previous studies in which 2.5 mmol/L calcium was used in the perfusate. Perfusion of isolated hearts with perfusate calcium concentrations up to 2.5 mmol/L (total) had no apparent detrimental effect on the stability of the preparation; however, a calcium concentration of 1.0 mmol/L resulted in a rapidly deteriorating preparation. In addition, under the conditions prevailing in the present study, a perfusate calcium content within the physiological range (1.4 mmol/L) appeared not to alter the vulnerability of the rat heart to injury during ischemia and reperfusion.The Canadian journal of cardiology 12/1991; 7(9):410-8. · 3.36 Impact Factor