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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 microM, 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.

Type

Journal article

Journal

Cardiovasc Res

Publication Date

06/2000

Volume

46

Pages

433 - 441

Keywords

4-Aminopyridine, Action Potentials, Animals, Anti-Arrhythmia Agents, Cell Size, Flecainide, Linear Models, Membrane Potentials, Patch-Clamp Techniques, Potassium Channel Blockers, Potassium Channels, Quinidine, Rabbits, Sinoatrial Node