ENHANCEMENT OF THE L-TYPE CA2-RABBIT CARDIAC MYOCYTES( CURRENT BY MECHANICAL STIMULATION IN SINGLE)

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 stimu lation on time-dependent currents, however, remain unsettled. Using th e whole-cell voltage-clamp method, we have found that mechanical stimu li enhance the L-type Ca2+ current (I-Ca,I-L) in rabbit cardiac myocyt es. At every membrane potential, (I-Ca,I-L) was reversibly increased b y osmotic cell swelling and by cell inflation caused by applying a pos itive pressure of 10 to 15 cm H2O via the patch pipette. I-Ca,I-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 sol ution containing 2 mmol/L Ca2+. The current-voltage relationship, the inactivation time constant, the steady state inactivation curve, and t he conductance properties of ICa,L were all virtually unaffected by me chanical stimulation except for the open probability, which appears to increase. The increase in I-Ca,I-L was not dependent on protein kinas e A, since an inhibitor peptide of cAMP-dependent protein kinase faile d to prevent the increase in I-Ca,I-L during mechanical stimuli (n = 5 ). The increase in I-Ca,I-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 effec t was not mediated by changes in intracellular Ca2+. Thus, mechanical stimulation due to cell swelling or inflation may itself directly incr ease I-Ca,I-L in rabbit cardiac myocytes.