Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes

Abstract

Single myocardial cells were enzymatically dispersed from guinea-pig atria and ventricles. At 25 degrees C, atrial cell action potentials differed significantly from ventricular cell action potentials in duration (atrial = 141 ms, ventricular = 497 ms) and over-shoot (atrial = +36 mV, ventricular = +42 mV). Action potentials of atrial and ventricular cells responded differently to changes in external K+ concentration ([K+]o). Elevation of [K+]o from 6 to 11 mM depolarized atrial cells but produced no significant change in action potential duration; similar changes in [K+]o depolarized ventricular cells and produced a significant shortening of the action potential duration. Voltage-clamp experiments were performed to investigate the ionic basis underlying the different action potential configurations of single atrial and ventricular myocytes. A single-micropipette voltage-clamp technique was used, employing either extremely small-tip diameter pipettes, without internal cell dialysis (Hume & Giles, 1983), or larger tip diameter pipettes, with internal dialysis (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). Two significant differences in background K+ conductance in single atrial and ventricular myocytes were observed: (i) the isochronal (5 s) current-voltage relationship of single ventricular myocytes exhibited a region of prominent negative slope conductance and elevation of [K+]o produced cross-over; a negative slope conductance region was absent in atrial cells and elevation of [K+]o produced very little cross-over of isochronal current-voltage relationships, and (ii) hyperpolarizing voltage pulses applied from holding potentials of -50 mV elicited inward current in ventricular cells which decayed with time; similar voltage-clamp pulses in atrial cells elicited inward currents which fail to decay. Single K+ channel current measurements confirmed the existence of different resting K+ channel properties in single atrial and ventricular myocytes. Resting K+ channels in both cell types had similar single channel conductances (30-32 pS with [K+]o = 145 mM) but ventricular K+ channels had significantly slower gating kinetics compared to atrial K+ channels (ventricular K+ channel mean open time = 223 ms; atrial K+ channel mean open time = 1 ms at Vr (resting membrane potential) -20 mV). The plateau and duration of the guinea-pig ventricular action potential was insensitive to high concentrations of tetrodotoxin (3 X 10(-5) M) but extremely sensitive to external Ca2+ concentration ([Ca2+]o). The second inward Ca2+ current (iCa) density was estimated in small atrial and ventricular myocytes of similar diameter and length.(ABSTRACT TRUNCATED AT 400 WORDS)