Journal of Neurophysiology, Vol 61, Issue 1 97-105, Copyright © 1989 by APS
Cyclic AMP selectively reduces the N-type calcium current component of mouse sensory neurons in culture by enhancing inactivation
R. A. Gross and R. L. Macdonald
Department of Neurology, University of Michigan Medical Center, Ann Arbor 48104.
1. The single-electrode voltage-clamp technique was used to assess the
effect of elevated intracellular cyclic AMP levels on the three calcium
current components of mouse dorsal root ganglion (DRG) neurons in culture.
2. Neither forskolin, cholera toxin, nor 8-Br-cyclic AMP affected the
isolated transient low-threshold (T) calcium current. 3. When calcium
currents were evoked at clamp potentials (Vc) positive to -20 mV from
holding potentials (Vh) near the resting membrane potential, the calcium
current consisted primarily of the transient high-threshold (N) and the
slowly inactivating high-threshold (L) calcium current components. Under
these conditions forskolin, cholera toxin, and 8-Br-cyclic AMP reduced the
peak calcium current but had little or no effect on the late (greater than
or equal to 300 ms) calcium current. When calcium currents were evoked from
very negative Vh, however, there was no effect of these compounds. 4.
Forskolin had no effect on the voltage-dependence of the current-voltage
relation, nor on the rate of recovery of the calcium current from
inactivation. 5. In other experiments, current traces were fitted using a
multiexponential curve-fitting program that determined the amplitudes and
inactivation time constants (tau i) of the three calcium current
components. Forskolin selectively reduced the magnitude of the
(curve-fitted) N current, and reduced its tau i. 6. Forskolin also enhanced
steady-state inactivation of the N current, producing a -7.5 mV shift in
the steady-state inactivation curve. 7. Cholera toxin, forskolin, and
8-Br-cyclic AMP had similar effects on calcium currents in mouse DRG
neurons in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
