Stimulation of phosphatidylinositol (PI) turnover may mediate the muscarinic suppression of the M-current in hippocampal pyramidal cells.
The mechanism involved in the muscarinic blockade of the M-current was examined in hippocampal pyramidal cells. Muscarinic agents which are full agonists at stimulating phosphatidylinositol (PI) turnover, such as oxotremorine-M, block the M-current, while those agents which are weak agonists, such as oxotremorine, had little effect on the M-current. These results strongly suggest that PI turnover is involved in the muscarinic blockade of the M-current. Although activation of protein kinase C failed to block the M-current, intracellular application of inositol trisphosphate (IP3) reproducibly reduced the M-current. Further experiments will be required to determine if the action of IP3 requires a rise in intracellular calcium.
Dutar
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Department of Pharmacology, University of California, San Francisco 94143.
Nicoll
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D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism* / Q000502:physiology; D011188:Potassium / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D010095:Oxotremorine; C042743:oxotremorine M; D002217:Carbachol; D011493:Protein Kinase C; D011188:Potassium