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.