Stretch‐activated anion currents of rabbit cardiac myocytes.

1. Stretch‐activated anion currents were studied in sino‐atrial and atrial cells using the whole‐cell patch clamp technique. With continuous application of positive pressure (5‐15 cmH2O) through the patch clamp electrode, the cell was inflated and the membrane conductance was increased. 2. Voltage clamp steps revealed that the stretch‐activated currents had time‐independent characteristics. The increase in membrane conductance was reversible on subsequent application of negative pressure to the electrode. 3. The reversal potential of the stretch‐activated currents was shifted by 60 mV for a 10‐fold change in intracellular Cl‐ concentration, while it was unaffected by replacement of Na+ in the extracellular solution by N‐methyl‐D‐glucamine. Cell superfusion with Cl(‐)‐deficient solution (10 mM Cl‐) reduced the amplitude of outward current. These findings indicate that the stretch‐activated conductance is Cl‐ selective. 4. The sequence of anion permeability through the stretch‐activated conductance was determined to be I‐(1.7) > NO3‐(1.5) > Br‐(1.2) > Cl‐(1.0) > and F‐(0.6). SCN‐ appeared to be more permeant than I‐. 5. The stretch‐activated conductance was reduced by the Cl‐ channel blockers, 4,4'‐dinitrostilbene‐2,2'‐disulphonic acid disodium salt, 4‐acetamido‐4'‐isothiocyanatostilbene‐2,2'‐disulphonic acid or anthracene‐9‐carboxylate (9‐AC). Administration of furosemide or bumetanide had no effect. 6. The stretch‐activated Cl‐ current was recorded even though intracellular Ca2+ ions were chelated by including 10 mM EGTA in the pipette solution. Neither the specific peptide inhibitor of cyclic AMP‐dependent protein kinase (50 microM), nor the non‐selective blocker of protein kinases, H‐7 (20 microM), was effective in reducing the stretch‐activated Cl‐ current, suggesting that the stretch‐activated Cl‐ current is a novel type of cardiac Cl‐ current, which shows a different modulatory mechanism from that of other cardiac Cl‐ currents.