Muscarinic regulation of the neuronal Na ⁺ /K ⁺ ‐ATPase in rat hippocampus

Key points Stimulation of postsynaptic muscarinic receptors was shown to excite principal hippocampal neurons by modulating several membrane ion conductances. We show here that activation also causes neuronal excitation inhibiting Na+/K+-ATPase activity. Muscarinic inhibition is mediated two separate signalling pathways lead downstream enhanced phosphorylation activating protein kinase C and G. through probably involved in cholinergic modulation activity may turn out be a widespread mechanism the brain. on enhances intrinsic excitability The electrogenic (NKA; ‘Na+ pump’) ubiquitous regulator excitability, generating hyperpolarizing current thwart excessive firing. Using electrophysiological pharmacological methodologies rat slices, we NKA pumping subjected regulation. muscarinic, but not nicotinic, activates membrane-bound phospholipase hydrolysis membrane-integral phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) inositol 1,4,5-triphosphate (IP3). Along one pathway, DAG (PKC). second IP3 Ca2+ release from endoplasmic reticulum, facilitating nitric oxide (NO) production. rise NO levels stimulates cGMP synthesis guanylate-cyclase, G (PKG). converge cause partial enzyme PKC PKG, leading marked increase excitability. This novel regulation contributes spatial navigation, learning memory.