Cyclic AMP selectively reduces the N-type calcium current component of mouse sensory neurons in culture by enhancing inactivation.
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)
Gross
R A
RA
Department of Neurology, University of Michigan Medical Center, Ann Arbor 48104.
Macdonald
R L
RL
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology; D006706:Homeostasis; D009475:Neurons, Afferent / Q000502:physiology*
D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D002118:Calcium