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)