Isolation and Characterization of a Persistent Potassium Current in Neostriatal Neurons. Nisenbaum, Eric S., Charles J. Wilson, Robert C. Foehring, and D. James Surmeier. Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee-Memphis,, Memphis, TN 38163.
APStracts 3:0076N, 1996.
1. Depolarization-activated, calcium-independent potassium (K + ) currents were studied using whole-cell voltage-clamp recording from neostriatal neurons acutely isolated from adult ( > 4 weeks old) rats. The whole-cell K + current was composed of transient and persistent components. The aims of the experiments were to isolate the persistent component and then to characterize its voltage-dependence and kinetics. 2. Application of 10 mM 4-aminopyridine (4-AP) completely blocked the transient currents while reducing the persistent current by approximately 40% (IC 50 of blockable current = 125 [mu]M). The persistent K + current also was reduced by tetraethylammonium (TEA). Two components to the TEA block were present having IC 50s of 125 [mu]M (23% of the blockable current) and 5.9 mM (77% of the blockable current). Collectively, these results suggested that the persistent component of the total K + current was pharmacologically heterogeneous. The properties of the 4-AP- r esistant, p ersistent K + current (I Krp ) were subsequently studied. 3. The kinetics of activation and deactivation of I Krp were voltage- dependent. Examination of the entire activation/deactivation time constant profile showed that it was bell-shaped with time constants being moderately rapid ( t 50 ms) at membrane potentials corresponding to the resting potential of neostriatal cells ( -80 mV), becoming considerably longer ( t 100 ms) at potentials near their spike thresholds ( -45 mV), and decreasing to a minimum ( t 5 ms) at potentials associated with the peak of their action potentials ( + 20 mV). The inactivation kinetics of I Krp also were voltage-dependent. The time constants of inactivation varied between 1 s and 8 s at potentials between -10 and +35 mV. 4. Unlike persistent K + currents in many other cell types, I Krp activated at relatively hyperpolarized membrane potentials ( -70 mV). The Boltzmann function describing activation had a half-activation voltage of -13 mV and a slope factor of 12 mV. In addition, the Boltzmann function describing the voltage-dependence of inactivation of I Krp had a relatively depolarized half-inactivation voltage of -55 mV and a large slope factor of 19 mV, indicating that this current was available over a broad range of membrane potentials (between -100 mV and -10 mV). 5. Neostriatal neurons recorded in vivo exhibit subthreshold shifts in membrane potential of variable duration (tens of milliseconds to seconds) from a hyperpolarized resting state to a depolarized state which is limited in amplitude just below spike threshold. The voltage-dependence of activation and inactivation of I Krp indicates that it will be available upon depolarization from the hyperpolarized state. However, the slow activation rate of this current suggests that it will contribute little either to limiting the amplitude of the initial depolarization associated with entry into the depolarized state or to depolarizing episodes of short duration (e.g., < 50 ms). However, I Krp should limit the amplitude of membrane depolarizations associated with prolonged excursions into the depolarized state.

Received 28 September 1995; accepted in final form 21 March 1996.
APS Manuscript Number J645-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96