ATP-Sensitive potassium channel function during the progression of pressure overload heart failure in rats / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate K(ATP) channel function of cardiomyocytes isolated from the left ventricular wall of rats with or without abdominal aortic constriction at different time points under normal or simulated ischemic conditions.</p><p><b>METHODS</b>Male Wistar rats were randomized into 4 groups (n = 10 - 13): 4-week sham-operated group (F4), 4-week aortic-banded group (T4), 12-week sham-operated group (F12), 12-week aortic-banded group (T12). Chronic pressure overload model was established by abdominal aortic constriction. Left ventricular myocytes were isolated by modified Langendorff perfusion method post in vivo hemodynamical measurements. The whole-cell patch-clamp technique was used to record transient outward current of K(ATP) channel on myocytes under normal and simulated ischemic perfusion conditions. The current densities of K(ATP) channel between F4 and T4 group, F12 and T12 group were compared under 0 mV of test potential.</p><p><b>RESULTS</b>SBP, DBP and MBP were significantly increased in T4 group compared to F4 group, but were similar between T12 and F12 groups. LVEDP and +/- dp/dtmax were similar between T4 and F4 groups and LVEDP was significantly increased while +/- dp/dtmax significantly reduced in T12 group than that in F12 group. Whole-cell membrane current densities were similar between F4 and T4 group or F12 and T12 group under normoxic condition, the K(ATP) current densities increased dramatically in T12 group [(28.11 +/- 3.91) pA/pF vs (11.55 +/- 1.17) pA/pF, P < 0.01], but not in T4 group [(14.09 +/- 5.74) pA/pF vs (11.74 +/- 3.68) pA/pF, P > 0.05] in myocytes exposed to ischemic solution for 25 minutes. The total number of K(ATP) channel in ventricular myocytes was similar between F4 and T4 group or F12 and T12 group.</p><p><b>CONCLUSIONS</b>The sarcolemmal K(ATP) channel was more sensitive to ischemia and the current magnitude was significantly increased at the stage of congestive heart failure. The functional change of K(ATP) channel occurred before the increase of total number of K(ATP) channel.</p>