Effects of Ca(2+)-channel drugs on K(+)-induced respiration in skeletal muscles.

Abstract

When skeletal muscles are exposed to elevations in extracellular K+, they experience a significant and long-lasting increase in O2 uptake. The basis for this response is unknown but may be related to an influx in extracellular Ca2+ ions during sarcolemmal depolarization. The purpose of this study was to determine if altering Ca2+ entry, either by removal of Ca2+ from the bathing fluid or by exposing muscles to selective Ca(2+)-channel agonists or antagonists, would affect K(+)-induced respiration. Isolated frog sartorii muscles were incubated in normal Ringer's solution (R) or a modified Ringer's containing 10 or 18 mM KCl. O2 uptake increased 83.7% in R+10 mM KCl and 502.2% in R+18 mM KCl. Incubation in Ca(2+)-free R+18 mM KCl containing Ni2+ in place of Ca2+ depressed the metabolic response to elevated K+. O2 uptake increased 234.5% in R+18 mM KCl containing Ni2+ and 80.6% in R+18 mM KCl containing Mg2+. Similarly, addition of the Ca(2+)-channel antagonists (gallopamil (D600) and diltiazem (DILT)) to R+18 mM KCl also depressed the respiratory response to elevated K+. O2 uptake increased 224.2% and 133.1% in R+18 mM KCL containing D600 and DILT, respectively. Conversely, addition of the Ca(2+)-channel agonists (Bay K 8644 (BAY) or palmitoyl carnitine (PC)) to R+10 mM KCl enhanced the metabolic response to elevated K+. O2 uptake increased 278% and 438.9% in R+10 mM KCl containing BAY and PC, respectively. These results indicate that the stimulatory effects of elevated extracellular K+ on skeletal muscle respiration are at least partially dependent on the availability of extracellular Ca2+ and its subsequent entry during membrane depolarization.