title: Time-dependent changes in kinetics of Na+ current in single canine cardiac Purkinje cells.
abstract: The spontaneous hyperpolarizing shift in Na+ channel kinetics that occurs during a series of voltage-clamp recordings was characterized in single canine cardiac Purkinje cells at 10-13.5 degrees C. The change in the half-point of voltage-dependent availability, in the half-point of peak conductance, in the voltage dependence of deactivation and time to peak Na+ channel current (INa), and in the time constants of INa decay in response to step depolarizations were examined. The half points of availability and conductance shifted similarly, -0.41 +/- 0.13 and -0.47 +/- 0.19 mV/min, respectively (n = 14). These were directly correlated (slope 1.14 +/- 0.06, R2 = 0.81) with conductance shifting on average only -0.05 mV/min faster than availability. The deactivation time constant-voltage relationship shifted similarly to availability and conductance. Tail current decay time constants predicted the voltage dependence of the open to closed transition to be 0.9e-. Time to peak INa in response to step depolarizations changed e-fold for 25 mV but plateaued at positive potentials (531 microseconds, n = 22). INa decay was multiexponential between -40 and 80 mV. Decay time constants changed little as a function of voltage at positive potentials. The contribution of the second time constant to decay amplitude was 15-20% over the entire voltage range. Time to peak INa shifted in a curvilinear fashion, changing less late in an experiment. We conclude that the channel-voltage sensor responds to a changing fraction of the applied voltage during an experiment, producing similar rates of shift of voltage-dependent availability, conductance, and deactivation time constants.
authors.affiliation: Department of Medicine, University of Chicago, Illinois 60637.
authors.forename: D A
authors.initials: DA
authors.lastname: Hanck
authors.forename: M F
authors.initials: MF
authors.lastname: Sheets
mesh_terms: D000818:Animals; D001682:Biological Availability; D002462:Cell Membrane / Q000502:physiology; D002469:Cell Separation; D004285:Dogs; D004553:Electric Conductivity; D004594:Electrophysiology; D007700:Kinetics; D008955:Models, Cardiovascular; D011690:Purkinje Fibers / Q000166:cytology / Q000502:physiology*; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism; D013997:Time Factors
chemical_list: D015222:Sodium Channels; D012964:Sodium