The relationship between Q gamma and Ca release from the sarcoplasmic reticulum in skeletal muscle.

Abstract

Asymmetric membrane currents and fluxes of Ca 2+ release were determined in skeletal muscle fibers voltage clamped in a Vaseline-gap chamber. The conditioning pulse protocol 1 for suppressing Ca z+ release and the "hump" component of charge movement current (I~), described in the first paper of this series, was applied at different test pulse voltages. The amplitude of the current suppressed during the ON transient reached a maximum at slightly suprathreshold test voltages (-50 to -40 mV) and decayed at higher voltages. The component of charge movement current suppressed by 20 I~M tetracaine also went through a maximum at low pulse voltages. This anomalous voltage dependence is thus a property ofI,, defined by either the conditioning protocol or the tetracaine effect. A negative (inward-going) phase was often observed in the asymmetric current during the ON of depolarizing pulses. This inward phase was shown to be an intramembranous charge movement based on (a) its presence in the records of total membrane current, (b) its voltage dependence, with a maximum at slightly suprathreshold voltages, (c) its association with a "hump" in the asymmetric current, (d) its inhibition by interventions that reduce the "hump," (e) equality of ON and OFF areas in the records of asymmetric current presenting this inward phase, and (f) its kinetic relationship with the time derivative of Ca release flux. The nonmonotonic voltage dependence of the amplitude of the hump and the possibility of an inward phase of intramembranous charge movement are used as the main criteria in the quantitative testing of a specific model. According to this model, released Ca 2÷ binds to negatively charged sites on the myoplasmic face of the voltage sensor and increases the local transmembrane potential, thus driving additional charge movement (the hump). This model successfully predicts the anomalous voltage dependence and all the kinetic properties of I~ described in the previous papers. It also Address reprint requests to Dr.

Kinetic isoforms of intramembrane charge in intact amphibian striated muscle.

“…The latter observations reinforced a scheme that required only a single (qt) intramembrane charge species that had a relatively shallow voltage dependence (k ~ 11-15 mV; Pizarro et al, 1991). This could trigger an initial release of intracellularly stored Ca z+ into the space between transverse tubules and sarcoplasmic membrane.…”

“…Such schemes were prompted by the observations of late inward-going phases that followed "humps" isolated from ON charge movement waveforms, as these could reflect the subsequent diffusion of Ca 2+ away from that space. There were also the complexities observed in the biphasic OFF charge movements and their smaller integrals compared with the ON transients Pizarro et al, 1991;Szucs et al, 1991;see also Hui, 1994). However, the experimental conditions adopted here resulted in complete decays to steady DC levels without intervening inward-going phases or other time-dependent currents.…”

“…The kinetic features such as dips or late time-dependent currents that have been reported elsewhere were absent (cf. Garcia et al, 1991;Pizarro et al, 1991;Csernoch et al, 1991). These findings prompted experiments that explored two major explanations for this antagonist action.…”

“…It was suggested that this complex behavior reflects a cooperative transition (see, e.g., Huang, 1983) that involves feedback systems driven by the release of Ca 2+ (an idea first suggested by Dr. W.K. Chandler, quoted in Horowicz and Schneider, 1981;see Csernoch et al, 1991;Pizarro et al, 1991). Alternatively, they could reflect intramembrane interactions involving the sensing units themselves (Huang, 1983(Huang, , 1984Hui and Chandler, 1990;Rios et al, 1993).…”

A slow component of intramembranous charge movement during sarcoplasmic reticulum calcium release in frog cut muscle fibers.

“…During the past 30 years, many properties of SR Ca release have been elucidated from studies on intact, cut, and skinned fibers, on iso-lated triads and SR vesicles, and on single SR Ca channels incorporated into lipid bilayers, as reviewed by Rios and Pizarro (1991), Schneider (1994), Meissner (1994), and Franzini-Armstrong andJorgensen (1994). The studies in intact and cut fibers have shown that the rate of Ca release from the SR into the myoplasm is under the control of the voltage across the membranes of the transverse tubular system.…”