Norepinephrine and cyclic adenosine 3':5'-cyclic monophosphate enhance a nifedipine-sensitive calcium current in cultured rat astrocytes.
We employed two microelectrode current-clamp and voltage-clamp methods to examine the modulation of Ca++ channels by norepinephrine and cyclic AMP (cAMP) in cultured astrocytes from the rat cerebral cortex. Currents owing to Ca++ channels were maximized by replacing Ca++ with Ba++ in the extracellular solution and pharmacologically blocking K+ and Na+ currents. In current-clamp experiments, we observed that norepinephrine, isoproterenol (an agonist of beta-receptors for norepinephrine), or dibutyryl cAMP (dbcAMP, a membrane permeant analogue of cAMP) induced or enhanced slow Ba++-dependent action potentials in the cells. In voltage-clamp experiments, we confirmed that the slow action potentials were generated by a voltage-activated and Ba++-dependent inward current. This current was mediated by channels that resembled L-type calcium channels (cf. McCleskey et al., Journal of Experimental Biology 124:177-190, 1986) in their voltage-activation range, slow inactivation, and sensitivity to blockage by Co++, Cd++, and nifedipine. DbcAMP, or isoproterenol, enhanced the Ba++ current. Modulation of Ca++ channel function in glial cells could have functional implications.
MacVicar
B A
BA
Neuroscience Research Group, University of Calgary, Alberta, Canada.
Tse
F W
FW
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001464:Barium / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats
D015220:Calcium Channels; D001464:Barium; D003994:Bucladesine; D009543:Nifedipine; D007545:Isoproterenol; D009638:Norepinephrine