2 COMPONENTS OF DELAYED RECTIFIER CURRENT IN CANINE ATRIUM AND VENTRICLE - DOES I-KS PLAY A ROLE IN THE REVERSE RATE DEPENDENCE OF CLASS-III AGENTS

Because the number and characteristics of delayed rectifier K+ current (I-K) components vary between species, the role of each component in the action potential and modulation by class III agents is uncertain. To address these issues, I-K was assessed in adult isolated canine ven tricular and atrial myocytes by using whole-cell and perforated-patch techniques. I-K components were characterized by using two complementa ry approaches: a kinetic approach (based on biexponential fits to deac tivating tail currents) and a pharmacological approach (using the meth anesulfonanilide compound E-4031). In ventricular myocytes, two expone ntial tail current components were distinguished; these components dif fered in the voltage and time dependence of activation and the effect of lower [K+](o). Both kinetic components contributed equally to peak tail current amplitude (measured at -35 mV) after a single 300-ms puls e to 5 mV, simulating an action potential. By use of E-4031, rapidly a nd slowly activating components of I-K (I-Kr and I-Ks respectively) th at were analogous to tail components described kinetically were identi fied. The activation kinetics and rectification properties of canine I -Kr and I-Ks are qualitatively similar to those described previously f or guinea pigs. In contrast, canine I-Kr and I-Ks deactivation kinetic s differed markedly from those found in guinea pigs, with canine I-Kr deactivating slowly (time constant tau, 2 to 3 s near -35 mV) and I-Ks deactivating rapidly (tau, 150 ms near -35 mV and decreasing to 30 ms near -85 mV). E-4031 elicited reverse rate-dependent effects (greater drug-induced prolongation of the action potential at slower stimulati on rates); this effect is inconsistent with the hypothesis attributing reverse rate dependence to incomplete I-Ks deactivation during rapid stimulation (due to rapid deactivation of canine I-Ks). Two I-K compon ents with characteristics comparable to those found in ventricular myo cytes were also observed in atrial myocytes. In conclusion, (1) I-Kr- and I-Ks-like components of I-K are present in canine atrial and ventr icular myocytes, with deactivation kinetics strikingly different from those found in guinea pigs, and (2) the rapid deactivation kinetics of canine I-Ks do not support its role in reverse rate dependence with c lass III agents in this species.