Inhibition of a cAMP-dependent Ca-activated K conductance by forskolin prolongs Ca action potential duration in lamprey sensory neurons.
Intracellular recordings from primary mechanosensory neurons (dorsal cells) of the lamprey spinal cord were made to test the membrane effects of forskolin, an activator of adenylate cyclase in these cells. At a concentration of 50 microM, forskolin was found to have a pronounced broadening effect on calcium action potentials (Ca APs) produced in the presence of voltage-activated K channel blockers (TEA, 3,4-DAP). Forskolin had no effect on passive membrane properties of the cells, such as resting potential or input resistance. Nor did it affect delayed rectification or Na APs and thus appeared not to block voltage-activated K channels. Forskolin's effect was evident only when a significant Ca component to the AP was present. It appeared not to increase the conductance of the Ca channel since its action was accompanied by a decrease in membrane conductance during the Ca AP, indicating instead an inhibition of a repolarizing Ca-activated conductance, other than a Ca-activated Cl conductance. The prolongation of Ca APs by forskolin, barium or the neurotransmitter GABA were all correlated in voltage-clamp with a decrease in outward current. Under the conductions used here, the major outward conductance in dorsal cells is a Ca-activated K conductance (gK(Ca]28, and it is concluded that the most probable mode of action for forskolin is via a cyclic AMP-mediated inhibition of this conductance. GABA has also been shown to prolong Ca APs in lamprey dorsal cells by inhibiting a repolarizing gK(Ca)28. Thus, the action of this transmitter may be mediated by an increase in intracellular cyclic AMP.
Womble
M D
MD
Department of Physiology, University of Colorado Health Sciences Center, Denver 80262.
Wickelgren
W O
WO
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D066298:In Vitro Techniques; D007798:Lampreys; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D015221:Potassium Channels; D005576:Colforsin; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D002122:Calcium Chloride; D011188:Potassium