title: Voltage-independent effects of extracellular K+ on the Na+ current and phase 0 of the action potential in isolated cardiac myocytes.
abstract: A rise in [K+]o, by depolarizing the resting membrane potential and partially inactivating the inward Na+ current (INa), is believed to play a critical role in slowing conduction during myocardial ischemia. In multicellular ventricular preparations, elevation of [K+]o has been suggested to decrease Vmax to a greater extent than expected from membrane depolarization alone. The mechanism of this voltage-independent effect of [K+]o is currently unknown, and its significance in single cardiac cells has not been determined. We have examined the voltage-independent effects of elevated [K+]o on INa and the action potential upstroke in isolated rabbit atrial and ventricular myocytes under voltage- and current-clamp conditions. Superfusate [K+] was varied from 5 mmol/L to 14 or 24 mmol/L, whereas [Na+] was maintained at 150 mmol/L. In cultured atrial cells and excised outside-out patches from freshly isolated atrial and ventricular cells, the amplitude and kinetics of INa were unchanged by elevation of [K+]o. In atrial cells, action potentials elicited from a holding potential of -70 mV had a similar Vmax (114.9 +/- 5.7 versus 112.2 +/- 4.8 V/s, mean +/- SEM, n = 6) and 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 holding potential of -70 mV, increasing [K+]o fro 5 to 14 mmol/L decreased Vmax from 161.8 +/- 18.0 to 55.3 +/- 5.0 V/s (n = 7, P < .001) and action potential amplitude from 128.1 +/- 1.3 to 86.6 +/- 5.4 mV (P < .001). This voltage-independent decrease in Vmax and action potential amplitude induced by elevated [K+]o was abolished in the presence of 1 mmol/L Ba2+, suggesting that it is attributable to an increased background K+ conductance. We conclude that elevation of [K+]o to levels expected during ischemia causes a marked voltage-independent depression of Vmax in ventricular cells, which may, in turn, contribute to the slowing of myocardial conduction characteristic of early ischemia.
authors.affiliation: Duke University Medical Center, Durham, NC 27710.
authors.forename: D W
authors.initials: DW
authors.lastname: Whalley
authors.forename: D J
authors.initials: DJ
authors.lastname: Wendt
authors.forename: C F
authors.initials: CF
authors.lastname: Starmer
authors.forename: Y
authors.initials: Y
authors.lastname: Rudy
authors.forename: A O
authors.initials: AO
authors.lastname: Grant
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D006352:Heart Ventricles; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000166:cytology; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D015222:Sodium Channels; D011188:Potassium