Impaired activation of ATP-sensitive K+ channels in endocardial myocytes from left ventricular hypertrophy

Junichi Shimokawa, Hisashi Yokoshiki, Hiroyuki Tsutsui

Research output: Contribution to journalArticle

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Abstract

ATP-sensitive K+ (KATP) 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 KATP 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 (IK,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 KATP channel opening (Timeonset 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 Timeonset 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 KATP channel activation in endocardial myocytes from SHR. In conclusion, KATP channel activation under metabolic stress was impaired in endocardial cells from rat hypertrophied left ventricle. The deficit of endocardial KATP channels to decreased intracellular ATP might contribute to the maladaptive response of hypertrophied hearts to ischemia.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number6
DOIs
Publication statusPublished - Dec 1 2007
Externally publishedYes

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Left Ventricular Hypertrophy
KATP Channels
Muscle Cells
Adenosine Triphosphate
Inbred WKY Rats
Physiological Stress
Heart Ventricles
Endocardium
Patch-Clamp Techniques
Myocardium
Homeostasis
Ischemia
Pathology
Glucose

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Impaired activation of ATP-sensitive K+ channels in endocardial myocytes from left ventricular hypertrophy. / Shimokawa, Junichi; Yokoshiki, Hisashi; Tsutsui, Hiroyuki.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 6, 01.12.2007.

Research output: Contribution to journalArticle

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