Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium.

Measurements of maximum upstroke velocity (Vmax) of guinea pig ventricular action potentials were used to investigate the effect of prolonged depolarization on the inactivation and recovery kinetics of cardiac sodium channels. Membrane potential before stimulated upstrokes was controlled by passing current across a sucrose gap. Two phases of inactivation ("slow" and "ultra-slow") having kinetics and voltage dependence different from the commonly observed fast inactivation process were observed. Ultra-slow inactivation developed exponentially with a time constant of several minutes between -60 and -20 mV. In contrast, slow inactivation developed with a time constant of 1-6 s between -60 and 40 mV. Under steady-state conditions slow and ultra-slow inactivations were virtually absent at -85 mV, while 50% of Vmax underwent slow inactivation at approximately 10 mV and 50% underwent ultra-slow inactivation at approximately -40 mV. Recovery from slow inactivation occurred exponentially with a time constant of about 2 s at -70 to -85 mV and 0.7 s at -100 mV. Recovery from ultra-slow inactivation was not completely characterized but was complete within 20 s at -85 mV. No significant effect of external [K+] (1-10 mM) on slow inactivation was found. The results suggest the existence of two additional inactivated states of the cardiac sodium channel distinctly different from the fast inactivated state.

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Kinetic analysis of mechanism of intestinal Na+-dependent sugar transport

AJP Cell Physiology ◽

10.1152/ajpcell.1985.248.5.c498 ◽

1985 ◽

Vol 248 (5) ◽

pp. C498-C509 ◽

Cited By ~ 23

Author(s):

D. Restrepo ◽

G. A. Kimmich

Keyword(s):

Experimental Data ◽

Steady State ◽

Sugar Transport ◽

Enzyme Kinetic ◽

Steady State Distribution ◽

State Distribution ◽

Least Squares Fit ◽

Coupling Stoichiometry ◽

Rate Limiting ◽

Kinetics Of

Zero-trans kinetics of Na+-sugar cotransport were investigated. Sugar influx was measured at various sodium and sugar concentrations in K+-loaded cells treated with rotenone and valinomycin. Sugar influx follows Michaelis-Menten kinetics as a function of sugar concentration but not as a function of Na+ concentration. Nine models with 1:1 or 2:1 sodium:sugar stoichiometry were considered. The flux equations for these models were solved assuming steady-state distribution of carrier forms and that translocation across the membrane is rate limiting. Classical enzyme kinetic methods and a least-squares fit of flux equations to the experimental data were used to assess the fit of the different models. Four models can be discarded on this basis. Of the remaining models, we discard two on the basis of the trans sodium dependence and the coupling stoichiometry [G. A. Kimmich and J. Randles, Am. J. Physiol. 247 (Cell Physiol. 16): C74-C82, 1984]. The remaining models are terter ordered mechanisms with sodium debinding first at the trans side. If transfer across the membrane is rate limiting, the binding order can be determined to be sodium:sugar:sodium.

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