A Na+-activated K+ current (I-K,I-Na) is present in guinea-pig but not ratventricular myocytes

The effects of removing extracellular Ca2+ and Mg2+ on the membrane potenti al, membrane current and intracellular Na+ activity (a(Na)(i)) were investi gated in guinea-pig and rat ventricular myocytes. Membrane potential was re corded with a patch pipette and whole-cell membrane currents using a single -electrode voltage clamp. Both guinea-pig and rat cells depolarize when the bathing Ca2+ and Mg2+ are removed and the steady-state a(Na)(i) increases rapidly from a resting value of 6.4 +/- 0.6 mM to 33 +/- 3.8 mM in guinea-p ig (n = 9) and from 8.9 +/- 0.8 mM to 29.3 +/- 3.0 mM (n = 5) in rat ventri cular myocytes. Guinea-pig myocytes partially repolarized when, in addition to removal of the bathing Ca2+ and Mg2+, K+ was also removed, however rat cells remained depolarized. A large diltiazem-sensitive inward current was recorded in guinea-pig and rat myocytes, voltage-clamped at -20 mV, when th e bathing divalent cations were removed. When the bathing K+ was removed af ter Ca2+ and Mg2+ depletion, a large outward K+ current developed in guinea -pig, but not in rat myocytes. This current had a reversal potential of -80 +/- 0.7 mV and was not inhibited by high Mg2+ or glybenclamide indicating that it is not due to activation of non-selective cation or adenosine triph osphate (ATP)-sensitive K channels. The current was not activated when Lireplaced the bathing Na+ and was blocked by R-56865, suggesting that it was due to the activation of K-Na channels.