The membrane mechanisms resulting in the movements of K+ and Cl- in normal skeletal muscle fibers of the frog are being studied. These two ions account for most of the membrane conductance in quiescent muscle fibers. In resting muscle the major passive pathway for K+ movement is the inward rectifier channel while the major pathway for Cl- movement is the external pH dependent Cl- channel. The pH dependent chloride channels in frog skeletal muscle appear to be principally located in the external surface of muscle cells with few such channels present in the membranes lining the transverse tubular system. Transmembrane chloride fluxes increase markedly when external pH is increased from 5.0 to 10.0 with a midpoint at about pH 6.8. The effects of external chloride concentration, membrane potential, and group specific chemical reagents on the pH dependence of chloride movements will be examined. In addition, the effects on Cl- movements of inorganic anions of the lyotropic series and various aromatic carboxylic acids will be studied at various external pHs, (Cl-)o, and membrane potentials and after chemical modification. The inward rectifier channels are located in the membranes covering the external surface of muscle cells as well as those lining the transverse tubular system. They provide the principal control for steady state membrane potential and, indirectly, other electrical properties of striated muscle under resting conditions. The rectifier channels will be studied in (1) whole sartorius muscles and in (2) single fibers under controlled membrane potentials where both the internal and external concentrations of different ions can be varied. The effects of other ions, such as Rb+ and Tl+, which both activate and inhibit potassium movements through the rectifier as well as moving through the rectifier channels themselves, will be studied. The modifications produced by various agents (i.e. quaternary onium ions) on this channel system will also be explored. The properties of the K+ inward rectifier are among the factors involved in hypotension and skeletal muscle weakness associated with hyperkalemia. Alteration of membrane conductance to chloride ions is one of the factors involved in some myotonias.
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