Alterations in atp-sensitive potassium channel sensitivity to atp in isolated cardiac myocytes from failing human hearts. Koumi, Shin-Ichi, Ruth L. Martin, and Ryoich Sato. Division of Cardiology, Department of Medicine and the Feinberg Cardiovascular Research Institute and the Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois, 60611, The Cardiac Electrophysiological Laboratories, University of Chicago, Chicago, Illinois, 60611 and The First Department of Medicine, Nippon Medical School, Tokyo 113, the First Department of Medicine, Kinki University Medical School, Osaka 589, Japan
APStracts 3:0479H, 1996.
Little is known about the involvement of preexisting heart disease on characteristics of ATP-sensitive K& channels (IK(ATP)) in human heart. We have characterized IK(ATP) in isolated cardiac myocytes from patients with congestive heart failure (HF) and compared these channel characteristics to those from donor hearts (healthy control) using the patch-clamp technique. During metabolic inhibition induced by treatment with cyanide (1 mM) and 2-deoxyglucose (10 mM), action potential shortening occurred in atrial myocytes isolated from both HF and donors, but this response was significantly greater and sooner in HF than in donors. The action potential duration at 90% repolarization was 24.7 +/- 4.1% (n=15) of control in HF, while it was 58.7 +/- 5.9% (n=10, p<0.001) of control in donors measured at 30 min metabolic inhibition. The shortening of the action potential was partially reversed by glibenclamide (0.5 _M) in both groups. Consistent with the action potential measurements, the whole-cell membrane current response to metabolic inhibition, evaluated by the differential current measurement, was sooner and greater in HF than in donors. Single channel atrial IK(ATP) from both HF and donors, recorded in the excised inside-out patch configuration, exhibited bursting opening, conductance and gating behaviors which did not differ between the two groups. However, the concentration of ATP at half-maximal inhibition (IC50) of the channel in HF was greater (131.0 _M) than in donors (26.1 _M). We conclude that IK(ATP) in cardiac myocytes from patients with HF has channel characteristics substantially similar to those in donors, but that the channel is less sensitive to ATP inhibition in HF than in donors. 

Received 29 August 1995; accepted in final form 15 October 1996.
APS Manuscript Number H818-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996