Histamine H1 receptors in C6 glial cells are coupled to calcium-dependent potassium channels via release of calcium from internal stores.
We investigated the action of histamine on C6-astroglioma cells using patch clamp recording and intracellular calcium measurement. Application of 100 microM histamine hyperpolarized the resting membrane potential and increased free intracellular calcium. Membrane hyperpolarization was accompanied by a decrease in input resistance. The effect of histamine was reversible and responses persisted following repeated applications. In voltage clamp experiments histamine elicited an outward current associated with a conductance increase and a reversal potential near the Nernst potential for potassium. The action of histamine was blocked by mepyramine but not by cimetidine or thioperamide suggesting that a H1 receptor mediated the response. Quinidine and charybdotoxin, but not apamin, blocked the hyperpolarization. Buffering internal calcium with BAPTA diminished the activation of the potassium channel, suggesting a calcium-dependent K(+)-channel, which was also found to be regulated by protein kinase C and phosphatases. The increase in intracellular calcium was not dependent on external calcium or sensitive to pertussis toxin, cholera toxin, forskolin or 8-bromo-cAMP. Both the hyperpolarization and the increase in intracellular calcium were blocked by thapsigargin or the phospholipase C inhibitor U73122. These results indicate that histamine liberates calcium from internal stores by activation of phospholipase C which in turn leads to an increase of intracellular Ca2+ and thereby to the activation of a calcium-dependent potassium channel in C6 glial cells.
Weiger
T
T
Heinrich-Heine-Universität Düsseldorf, Institute of Physiology II, Germany.
Stevens
D R
DR
Wunder
L
L
Haas
H L
HL
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
D015221:Potassium Channels; D011969:Receptors, Histamine H1; D019204:GTP-Binding Proteins; D002118:Calcium