Journal of Neuroscience, Vol 15, 3927-3935, Copyright © 1995 by Society for Neuroscience
Modulation of the inactivation of voltage-dependent potassium channels by cAMP
S Chung and LK Kaczmarek
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Modulation of voltage-dependent potassium currents can alter the shape and
timing of action potentials, thereby altering neurotransmitter release. To
examine the effect of a cAMP analog on potassium currents in metabolically
intact cells, perforated-patch and cell-attached patch recordings were
carried out using the GH4C1 pituitary cell line. A major component of
voltage-dependent potassium current in these cells inactivates slowly, with
a time constant of several seconds. Application of dibutyryl cAMP decreased
this current at voltages positive to -10 mV and increased the rate of
inactivation by approximately twofold. Single channel recordings revealed
two channel types whose voltage dependence and kinetics of inactivation
match those of the macroscopic current. One of these, the smaller
conductance (7.5 pS) channel, was sensitive to the cAMP analog, which
decreased the latency of the channel to enter a long-lasting inactivated
state. Ensemble averages of the activity of this channel showed that,
consistent with its effect on the macroscopic current, dibutyryl cAMP
increased its rate of inactivation. Somatostatin, an agent that is known to
activate a serine/threonine phosphatase in these cells, completely reversed
the effect of dibutyryl cAMP on the channel, while the cyclic GMP analog,
dibutyryl cyclic GMP was without effect. In contrast, the rate of
inactivation of the larger conductance (approximately 19 pS) channel was
not accelerated by dibutyryl cAMP. These studies indicate that different
channel subtypes expressed in a single cell respond differently to
elevations of cAMP, and suggest that the overall response of potassium
currents to second messengers may be determined by the ratio of different
channel subtypes.