Neurotransmitter-induced novel modulation of a nonselective cation channel by a cAMP-dependent mechanism in rat pineal cells.
In the rat, circadian rhythm in melatonin is regulated by noradrenergic and neuropeptide inputs to the pineal via adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca2+-dependent mechanisms. We have identified a large conductance (170 pS), voltage-dependent, nonselective cation channel on rat pineal cells in culture that shows a novel mode of modulation by cAMP. Pituitary adenylate cyclase activating peptide (PACAP), norepinephrine, or 8-Br-cAMP increase channel open probability (Po) with a hyperpolarizing shift in voltage dependence such that the channel becomes active at resting membrane potentials. The increase in Po was accompanied by a change in current rectification properties such that the channel was transformed from being inactive at rest to an inwardly rectifying cation conductance in the presence of agonist, which depolarizes the cell. This channel is calcium insensitive, is blocked by Cs+, and shows a permeability sequence: K+ > Na+ >/= NH+4 > Li+. The data suggest that PACAP and norepinephrine acting through a cAMP-dependent mechanism modulate this nonselective cation channel, resulting in a slow onset depolarization that may be important in regulation of pineal cell excitability.
Darvish
N
N
Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Russell
J T
JT
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010870:Pineal Gland / Q000166:cytology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology*
C495403:Adcyap1 protein, rat; D002412:Cations; D007473:Ion Channels; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D009638:Norepinephrine