Page 38 - F. Cell biology

[F. Cell biology-23]

Effects of acebutolol on cardiac action potential and human

ERG K+ Current

Su-Hyun Jo¹

¹Department of Physiology, Institute of Bioscience and Biotechnology, BK21 plus Graduate Program, Kangwon

National University College of Medicine, Chuncheon 200-701, Korea

K+ channels are key components of the primary and secondary basolateral Cl- pump systems, which are important
for secretion from the salivary glands. Acebutolol is a cardioselective beta blocker with ISA (intrinsic

sympathomimetic activity). We studied the effects of acebutolol on a human K+ channel, human ether-a-go-go-

related gene (hERG), expressed in Xenopus oocytes and on action potential of guinea pig ventricular myocytes. The
hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier K+ channel in the heart.
Mutations in hERG reduce IKr and cause type 2 long QT syndrome, a disorder that predisposes individuals to life-

threatening arrhythmias. Acebutolol decreased hERG current amplitude at the end of the voltage steps, however,
the drug failed to induce a concentration-dependent changes hERG tail currents. Acebutolol did not change the

value of V1/2 for activation curve of hERG tail current, indicating the drug did not affect activation gating. In guinea
pig ventricular myocytes, acebutolol did not change the resting membrane potential, however, the drug increased

the action potential amplitude, action potential duration (APD₉₀, APD₂₀), showing that acebutolol could change
cardiac electrophysiology function.