Alpha1‐Adrenergic Receptor Modulation of Repolarization in Canine Purkinje Fibers

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Abstract
Alpha‐Agonists and Repolarization. Introduction: Alpha‐adrenergic receptor stimulation increases contractility and prolongs repolarization. These effects are modulated by α1‐adrenergic receptor‐mediated inhibition of transsarcolemmal potassium currents. Methods and Results: We used standard microelectrode techniques to study the actions of 4‐aminopyridine (4‐AP), which blocks the transient outward current, Ito, and WAY‐123,398, which blocks the delayed rectifier, Ik, on canine Purkinje fiber action potential prolongation induced by phenylephrine. At a basic cycle length of 1 second, phenylephrine (0.1 to 10 μ) dose‐dependently prolonged action potential duration at 90% repolarization (APD90) from 331 ± 10 msec to 400 ± 12 msec (P < 0.05) at phenylephrine, 10 μ. Phenylephrine did not change phase 1 or plateau height. 4‐AP (0.1 mM) decreased phase 1 magnitude, shifted plateau height to more positive potentials (from 0.1 ± 1.8 mV to 14.3 ± 1.1 mV [P < 0.05]), and shortened APD90 from 318 ± 9 msec to 294 ± 8 msec (P < 0.05). 4‐AP did not block phenylephrine effects on APD90, which increased, at 10 μ phenylephrine, from 294 ± 8 msec to 342 ± 6 msec (P < 0.05). In contrast, WAY‐123,398 (0.1 μ) prolonged APD90 from 360 ± 6 msec to 452 ± 6 msec (P < 0.05), and had no effect on plateau height. In the presence of WAY‐123,398, phenylephrine no longer increased APD9o. Conclusion: (1) Agents that block Ito shorten APD in Purkinje fibers; and (2) the α‐agonist mediated increase of APD in canine Purkinje fibers can be explained by inhibition of Ik.

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