title: Na/Ca exchange and excitation--contraction coupling in frog fast fibres.
abstract: A 3 Na/Ca exchanger in the transverse tubular wall is modelled as the coupling mechanism between transverse tubular depolarization and Ca release from the sarcoplasmic reticulum. At rest, the Ca-occupied site faces the transverse tubular lumen. Upon depolarization, the difference in chemical potentials of Na and Ca gives a net inward force on Ca resulting in a reorientation of the exchanger so the Ca site now faces the myoplasm and releases Ca to stimulate Ca-induced Ca release from the sarcoplasmic reticulum. The rotation of the exchanger's asymmetrical charge could generate the 'charge movement' signal. As depolarization continues, the site is depleted of Ca and contraction ends spontaneously. Repolarization reorients the exchanger; the depleted Ca site now faces the transverse tubular lumen and slowly refills with Ca (repriming). A kinetic model is capable of controlling both twitch and contracture tension. The Na/Ca exchange blocker dichlorobenzamil (Merck) (10 microM), elevated external Na and low pH all slowed the rate of rise of potassium contracture tension. The ratios of rates of tension rise were dCB/control = 0.4 +/- 0.1, elevated external Na/Tris = 0.6 +/- 0.1, pH 6.3/control = 0.7 +/- 0.01. These results can be mimicked with the kinetic model by slowing the rate of 'rotation' (and hence charge movement) by 50%. Elevated internal Na increases the rate of rise of contracture tension; elevated internal Na/control 1.6 +/- 0.3. Dichlorobenzamil also slows the recovery following spontaneous relaxation; the time constant (68 s) of repriming is unchanged but shifted to longer recovery times. Reduced external Na and pH 6.3 also slow recovery in a similar manner, consistent with delayed rotation of the Ca-depleted site. These results suggest that Na/Ca exchange is a step in both the excitation contraction coupling chain and the repolarization-repriming sequence.
authors.affiliation: Department of Basic Sciences, University of Illinois College of Medicine at Peoria, IL 61656.
authors.forename: B A
authors.initials: BA
authors.lastname: Curtis
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D002462:Cell Membrane / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000648:ultrastructure; D011898:Ranidae / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: C041470:3',4'-dichlorobenzamil; D000584:Amiloride; D012964:Sodium; D002118:Calcium