Effects of intracellular pH and [Mg2+] on excitation-contraction coupling in skeletal muscle fibres of the rat.

1. The effects on normal excitation-contraction (E-C) coupling of two important intracellular ions, H+ and Mg2+, were examined in skinned fibres from the extensor digitorum longus muscle of rat. 2. A single depolarization (2-3 s duration) in the presence of 1 mM Mg2+ (pH 7.1, 23 degrees C) released most of the available Ca2+ in the sarcoplasmic reticulum (SR), but a similar depolarization in the presence of 10 mM Mg2+ was unable to release almost any Ca2+. Thus, raised [Mg2+] potently inhibits depolarization-induced Ca2+ release in mammalian muscle. 3. Depolarization at pH 6.2 (1 mM Mg2+, 23 degrees C) induced a large force response, which was on average 78 +/- 2%, n = 6, of the depolarization-induced response at pH 7.1; this reduction resulted from a corresponding reduction in maximum Ca(2+)-activated force at pH 6.2. Similar results were obtained at 37 degrees C. Also, a single depolarization at pH 6.2 caused almost complete depletion of the releasable Ca2+ in the SR. Thus, low pH does not prevent depolarization-induced Ca2+ release in mammalian muscle. 4. Lowering the free [Mg2+] from 1 mM to 15 microM caused massive release of Ca2+, and depletion of the SR, at both pH 7.1 and 6.2, indicating that over this pH range, H+ did not readily substitute for Mg2+ at its inhibitory site on the Ca2+ release channel.(ABSTRACT TRUNCATED AT 250 WORDS)