Enhancement of the L-type Ca2+ current by mechanical stimulation in single rabbit cardiac myocytes

Anion conductance is known to be activated by mechanical stimulation, such as osmotic cell swelling or cell inflation via the patch pipette, of canine or rabbit cardiac myocytes. The effects of mechanical stimulation on time-dependent currents, however, remain unsettled. Using the whole-cell voltage-clamp method, we have found that mechanical stimuli enhance the L-type Ca2+ current (ICa,L) in rabbit cardiac myocytes. At every membrane potential, ICa,L was reversibly increased by osmotic cell swelling and by cell inflation caused by applying a positive pressure of 10 to 15 cm H2O via the patch pipette. ICa,L was increased during cell inflation by 37 +/- 21% (mean +/- SD, n = 17) in atrial cells and by 37 +/ -8% (n = 7) in sinoatrial node cells in solution containing 2 mmol/L Ca2+. The current-voltage relationship, the inactivation time constant, the steady state inactivation curve, and the conductance properties of ICa,L were all virtually unaffected by mechanical stimulation except for the open probability, which appears to increase. The increase in ICa,L was not dependent on protein kinase A, since an inhibitor peptide of cAMP-dependent protein kinase failed to prevent the increase in ICa,L during mechanical stimuli (n=5). The increase in ICa,L caused by cell inflation was unaffected by the chelation of intracellular Ca2+ by the addition of 10 mmol/L EGTA or 10 mmol/L BAPTA to the pipette solution, suggesting that the effect was not mediated by changes in intracellular Ca2+. Thus, mechanical stimulation due to cell swelling or inflation may itself directly increase ICa,L in rabbit cardiac myocytes.