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Alpha 1-adrenergic receptor modulation of repolarization in canine Purkinje fibers
1Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York.
Introduction:
Alpha 1-adrenergic receptor stimulation increases contractility and prolongs repolarization. These effects are modulated by alpha 1-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, I(to), 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 microM) dose-dependently prolonged action potential duration at 90% repolarization (APD90) from 331 +/- 10 msec to 400 +/- 12 msec (P < 0.05) at phenylephrine, 10 microM. 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 microM phenylephrine, from 294 +/- 8 msec to 342 +/- 6 msec (P < 0.05). In contrast, WAY-123,398 (0.1 microM) 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 APD90.
Conclusion:
(1) Agents that block I(to) shorten APD in Purkinje fibers; and (2) the alpha-agonist mediated increase of APD in canine Purkinje fibers can be explained by inhibition of Ik.