Mitochondria are the main ATP source for a cytosolic pool controlling the activity of ATP-sensitive K(+) channels in mouse cardiac myocytes.

OBJECTIVE

The aim was to identify the major ATP source controlling the activity of sarcolemmal K(ATP) channels in ventricular cardiomyocytes.

METHODS

K(ATP)-channel current (I(KATP)) was measured with the patch-clamp technique in either the whole-cell (glycogenolysis blocked by 10 mmol/l EGTA), cell-attached, or inside-out configuration.

RESULTS

In the absence of any substrate, I(KATP) (amplitude 31+/-4 nA; n=5) appeared spontaneously 520+/-160 s (n=6) after whole-cell access. This latency was shortened by exposure to anoxia (117+/-33 s, n=32) and even more by uncoupling (1-10 micromol/l FCCP; 25+/-3 s; n=13) while the amplitude was unchanged. During metabolic inhibition the latency was remarkably prolonged when the F1F0-ATPase was blocked by oligomycin, suggesting that under those conditions the F1F0-ATPase is the major ATP consumer. Glucose (5.5-20.0 mmol/l) in the bath solution did not affect the amplitude of I(KATP) but prolonged its latency compared to respective substrate-free conditions. However, I(KATP) was blocked immediately by mitochondrial substrates. FCCP also induced large I(KATP) in cell-attached measurements in either the absence or presence of glucose and oligomycin.

CONCLUSIONS

The activity of K(ATP) channels in cardiomyocytes of mice is controlled by a cytosolic [ATP] pool for which oxidative phosphorylation is the predominant ATP source.