Characterisation of the transient outward K+ current in rabbit sinoatrial node cells

Objective: To (i) characterise the electrophysiological and pharmacological properties of the transient outward K+ current, I-to, (ii) determine the relationship between the density of I-to and cell size, and (iii) determine the role of I-to in electrical activity in rabbit sinoatrial node cells at 35 degrees C. Methods: Rabbit sinoatrial node cells were studied using whole-cell voltage and current clamp techniques. Results: I-to showed half activation and inactivation at +11 and -49 mV, respectively. I-to was blocked by 4-aminopyridine (4-AP) as well as the class I agents, quinidine and flecainide, with EC50 values of 326, 21 and 19 mu M, respectively. The densities of the transient and sustained components of 4-AP-sensitive current were significantly correlated with cell capacitance, a measure of cell size, and were greater in cells with a larger capacitance. Block of I-to by 4-AP affected both the action potential and pacemaker activity of sinoatrial node cells and the effects were greater in cells with a larger capacitance. Conclusions: I-to in sinoatrial node cells shows similar electrophysiological and pharmacological properties to I-to in atrial and ventricular cells. The expression of I-to in sinoatrial node cells is heterogeneous and differs in large and small cells (likely to be from the periphery and centre of the sinoatrial node, respectively). I-to plays an important role in action potential configuration and pacemaker activity in sinoatrial node cells, especially in larger cells. (C) 2000 Elsevier Science B.V. All rights reserved.