Role of the 293b-sensitive, slowly activating delayed rectifier potassium current, i , in pacemaker activity of rabbit isolated

Objectives: (i) to characterize the electrophysiological properties of the slowly activating delayed rectifier potassium current, i , Ks defined as the 293b-sensitive current, during the action potential (AP) of rabbit sino-atrial node (SAN) pacemaker cells; (ii) to evaluate the contribution of i to the pacemaker AP under physiological conditions and during b-adrenergic stimulation. Methods: Rabbit SAN Ks pacemaker cells were studied using the perforated patch clamp technique in voltage-, AP- and current-clamp modes. Results: Voltage-clamp findings . Block of i by 293b is dose-dependent, with an IC (half block) in rabbit SAN cells of 1.35 mM and an IC Ks 50 80 (sub-maximal block) of 5 mM. Sub-maximal concentrations of 293b have no significant effects on long-lasting and transient inward calcium currents, i and i , inward hyperpolarization activated current, i , and transient outward current, i . AP-clamp experiments. Ca,L Ca,T f to The 293b-sensitive current activates near the peak of the SAN pacemaker action potential, reaches a mean maximal current density of 1.060.3 pA / pF (n58, cell capacitances 27 to 62 pF, mean 3564.0 pF) during late repolarization, and inactivates towards the end of repolarization. Additionally, in two smaller cells (cell capacitances 15 and 23 pF), no discernible 293b-sensitive current component was detected. Current-clamp data. In spontaneously beating SAN cells under control conditions, sub-maximal block of i by 5 mM 293b has Ks negligible effects on action potential characteristics and does not change average cycle length ( n511). In contrast, after pre-treatment with 10 nM isoprenaline to mimic b-adrenergic stimulation, cells showed a 293b-induced depolarization of maximum diastolic potential by 2.261%, a decrease in diastolic depolarization rate by 9.964%, and a slowing of late action potential repolarization by 28.7610.2%, resulting in a prolongation of spontaneous cycle length by 9.863.0% (P,0.05, n510; for all parameters). Conclusion: Our findings suggest that in rabbit SAN: (i) i is activated during the normal pacemaker AP; (ii) the contribution of i to beating rate is small under Ks Ks control conditions; and (iii) i contributes significantly to spontaneous pacemaker rate during b-adrenergic stimulation. © 2002 Ks