The serotonin inhibition of high-voltage-activated calcium currents is relieved by action potential-like depolarizations in dissociated cholinergic nucleus basalis neurons of the guinea-pig.
The aim of the present study was to investigate whether the voltage-dependent inhibition of calcium currents by serotonin 5-HT1A agonists can be alleviated (facilitated) by action potential-like depolarizations. In dissociated cholinergic basal forebrain neurons using whole-cell recordings, it is shown that a selective serotonin 5-HT1A agonist (8-OH-DPAT) predominantly blocks N-type HVA calcium current, although a minor reduction of P-type current was also observed. The inhibition may principally occur through Gi-Go subtypes of G-proteins because it was prevented by N-ethylmaleimide, a substance known to block specifically pertussis-sensitive G-proteins. The inhibitory effect of 8-OH-DPAT on calcium currents is voltage-dependent because it was alleviated by long-lasting depolarizing prepulses. Interestingly, the inhibition could also be reversed by prepulses made-up of action potential-like depolarizations that were given at a frequency of 200 Hz. This observation may have important implications during periods of high-frequency rhythmic bursts, a firing pattern that is prevalent in cholinergic basal forebrain neurons.
Williams
S
S
Département de Physiologie, Centre Médical Universitaire, Genève, Switzerland.
Serafin
M
M
Mühlethaler
M
M
Bernheim
L
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D004558:Electric Stimulation; D006168:Guinea Pigs; D010455:Peptides / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D013377:Substantia Innominata / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D011985:Receptors, Serotonin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D020866:omega-Conotoxin GVIA