Opening of dihydropyridine calcium channels in skeletal muscle membranes by inositol trisphosphate

Abstract

In many non-muscle cells^1,2, D-inositol 1,4,5-trisphosphate (InsP₃) has been shown to release Ca²⁺ from intracellular stores, presumably from the endoplasmic reticulum. It is thought to be a ubiquitous second messenger that is produced in, and released from, the plasma membrane in response to extracellular receptor stimulation. By analogy, InsP₃ in muscle cells has been postulated to open calcium channels in the sarcoplasmic reticulum (SR) membrane, which is the intracellular Ca²⁺ store that releases Ca²⁺ during muscle contraction^3,4. We report here that InsP₃ may have a second site of action. We show that InsP₃ opens dihydropyridine-sensitive Ca²⁺ channels in a vesicular preparation of rabbit skeletal muscle transverse tubules^5–10. InsP₃-activated channels and channels activated by a dihydropyridine agonist in the same preparation have similar slope conductance and extrapolated reversal potential and are blocked by a dihydropyridine antagonist. This suggests that in skeletal muscle, InsP₃ can modulate Ca²⁺ channels of transverse tubules from plasma membrane, in contrast to the previous suggestion that the functional locus of InsP₃ is exclusively in the sarcoplasmic reticulum membrane.