Impaired activation of ATP-sensitive K+ channels in endocardial myocytes from left ventricular hypertrophy.
ATP-sensitive K(+) (K(ATP)) channels are essential for maintaining the cellular homeostasis against metabolic stress. Myocardial remodeling in various pathologies may alter this adaptive response to such stress. It was reported that transmural electrophysiological heterogeneity exists in ventricular myocardium. Therefore, we hypothesized that the K(ATP) channel properties might be altered in hypertrophied myocytes from endocardium. To test this hypothesis, we determined the K(ATP) channel currents using the perforated patch-clamp technique, open cell-attached patches, and excised inside-out patches in both endocardial and epicardial myocytes isolated from hypertrophied [spontaneous hypertensive rats (SHR)] vs. normal [Wistar-Kyoto rats (WKY)] left ventricle. In endocardial cells, K(ATP) channel currents (I(K,ATP)), produced by 2 mM CN(-) and no glucose at 0 mV, were significantly smaller (P < 0.01), and time required to reach peak currents after onset of K(ATP) channel opening (Time(onset to peak)) was significantly longer (319 +/- 46 vs. 177 +/- 37 s, P = 0.01) in the SHR group (n = 9) than the WKY group (n = 13). However, in epicardial cells, there were no differences in I(K,ATP) and Time(onset to peak) between the groups (SHR, n = 12; WKY, n = 12). The concentration-open probability-response curves obtained during the exposure of open cells and excised patches to exogenous ATP revealed the impaired K(ATP) channel activation in endocardial myocytes from SHR. In conclusion, K(ATP) channel activation under metabolic stress was impaired in endocardial cells from rat hypertrophied left ventricle. The deficit of endocardial K(ATP) channels to decreased intracellular ATP might contribute to the maladaptive response of hypertrophied hearts to ischemia.
Shimokawa
Junichi
J
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
Yokoshiki
Hisashi
H
Tsutsui
Hiroyuki
H
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003486:Cyanides / Q000494:pharmacology; D004195:Disease Models, Animal; D004699:Endocardium / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D006352:Heart Ventricles / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D003486:Cyanides; D054086:KATP Channels; D000255:Adenosine Triphosphate; D005947:Glucose