Journal of Neuroscience, Vol 14, 7713-7725, Copyright © 1994 by Society for Neuroscience
Facilitation of calcium-dependent potassium current
SH Thompson
Department of Biological Sciences, Stanford University, Pacific Grove, California 93950.
The activation of Ca-dependent K+ current, Ic, was studied in macropatches
on the cell bodies of molluscan neurons. When a depolarizing voltage-clamp
pulse was applied repeatedly, Ic facilitated in a manner that resembled the
facilitation of synaptic transmitter release. Facilitation was
characterized by an increase in Ic amplitude, a progressive increase in
instantaneous outward current, and a decrease in utilization time.
Experiments were done to investigate the mechanism responsible for Ic
facilitation. Facilitation was reduced by microinjection of an exogenous
Ca2+ buffer into the cytoplasm, indicating that facilitation is a
Ca(2+)-dependent process. It was also reduced at elevated temperatures.
Conversely, facilitation was greatly potentiated by blocking the Na/Ca
exchange mechanism. It is concluded that the facilitation of Ca-dependent
K+ current results from the accumulation of Ca2+ at the inner face of the
membrane during the repeated activation of Ca2+ channels by depolarization.
The Ca2+ indicator fluo-3 was used in fluorescence imaging experiments to
measure changes in [Ca]i near the cell membrane during repeated
depolarizing pulses and the interpretation of these results was aided by
numerical simulations of Ca2+ accumulation, diffusion, and buffering in the
peripheral cytoplasm. These experiments showed that the time course of Ic
facilitation matches the time course of Ca2+ accumulation at the membrane.
It was found that the strength of Ic facilitation varies among patches on
the same neuron, suggesting that the accumulation of Ca2+ is not uniform
along the inner surface of the membrane and that gradients in [Ca]i develop
and are maintained during trains of depolarizing pulses. Potential
mechanisms that may lead to local differences in Ca2+ accumulation and Ic
facilitation are discussed.
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