Isolation and Characterization of a Persistent Potassium Current in
Nisenbaum, Eric S., Charles J. Wilson, Robert C. Foehring, and D. James
Department of Anatomy and Neurobiology, College of Medicine, University of
Tennessee-Memphis,, Memphis, TN 38163.
APStracts 3:0076N, 1996.
SUMMARY AND CONCLUSIONS
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