Chronic loss of KATP channel activity results in an increase Ca2+ sensitivity during tetanic contractions.

Abstract

The ATP‐sensitive K+ channel (KATP channel) is essential in preventing large increases in unstimulated [Ca2+]i and unstimulated force during fatigue (Cifelli et al. 2007. J. Physiol. 582:843) because of an excess Ca2+ influx through L‐type Ca2+ channels. The objective of this study was to determine whether a difference in Ca2+ sensitivity could be observed in unfatigued KATP channel deficient muscle. FDB bundles from CD‐1 mice (wild type) and from null mice for the Kir6.2 gene (Kir6.2−/− mice), which encodes for the protein making the pore of the channel, were used in this study. Lowering the [Ca2+]e from 2.4 to 0.6 mM had no effect on the peak tetanic force‐stimulus strength relationship of wild type FDBs as expected from previous studies. However, the relationship was shifted toward higher voltages in Kir6.2−/− FDBs. Addition of verapamil, a L‐type Ca2+ channel blocker, significantly reduced peak tetanic force at 2 μM in wild type FDBs, while it did the same at 0.5 μM in Kir6.2−/−FDBs. Verapamil also caused greater fade in Kir6.2−/− than wild type FDBs. Acutely blocking KATP channel in wild type FDBs with 10 μM glibenclamide did not affect the verapamil sensitivity. The results suggest that a chronic loss of KATP channel activity results in an increased needs for Ca2+ influx to generate and maintain force during a tetanic contraction.