VOLTAGE-INDEPENDENT EFFECTS OF EXTRACELLULAR K-0 OF THE ACTION-POTENTIAL IN ISOLATED CARDIAC MYOCYTES( ON THE NA+ CURRENT AND PHASE)

A rise in [K+](o), by depolarizing the resting membrane potential and partially inactivating the inward Na+ current (I-Na), is believed to p lay a critical role in slowing conduction during myocardial ischemia. In multicellular ventricular preparations, elevation of [K+](o) has be en suggested to decrease V-max to a greater extent than expected from membrane depolarization alone. The mechanism of this voltage-independe nt effect of [K+](o) is currently unknown, and its significance in sin gle cardiac cells has not been determined. We have examined the voltag e-independent effects of elevated [K+](o) on I-Na and the action poten tial upstroke in isolated rabbit atrial and ventricular myocytes under voltage- and current-clamp conditions. Superfusate [K+] was varied fr om 5 mmol/L to 14 or 24 mmol/L, whereas [Na+] was maintained at 150 mm ol/L. In cultured atrial cells and excised outside-out patches from fr eshly isolated atrial and ventricular cells, the amplitude and kinetic s of I-Na were unchanged by elevation of [K+](o). In atrial cells, act ion potentials elicited from a holding potential of -70 mV had a simil ar V-max (114.9 +/- 5.7 versus 112.2 +/- 4.8 V/s, mean +/- SEM, n=6) a nd action potential amplitude (115.0 +/- 2.4 versus 113.4 +/- 3.9 mV) in 5 and 24 mmol/L [K+](o). In contrast, in ventricular cells at a hol ding potential of -70 mV, increasing [K+](o) from 5 to 14 mmol/L decre ased V-max from 161.8 +/- 18.0 to 55.3 +/- 5.0 Vis (n=7, P<.001) and a ction potential amplitude from 128.1 +/- 1.3 to 86.6 +/- 5.4 mV (P<.00 1). This voltage-independent decrease in V-max and action potential am plitude induced by elevated [K+](o) was abolished in the presence of 1 mmol/L Ba2+, suggesting that it is attributable to an increased backg round K+ conductance. We conclude that elevation of [K+](o) to levels expected during ischemia causes a marked voltage-independent depressio n of V-max in ventricular cells, which may, in turn, contribute to the slowing of myocardial conduction characteristic of early ischemia.