Phospholipase C-mediated inhibition of the M-potassium current by muscarinic-receptor activation in the vestibular primary-afferent neurons of the rat.

The activation of the efferent vestibular system modifies the basal discharge and the dynamic response of primary-afferent neurons to head motion and gravitational stimuli. The efferent input to afferent neurons is mediated primarily by cholinergic synapses that activate both muscarinic and nicotinic receptors. Previously we had shown that the muscarinic-acetylcholine-receptor (mAChR) activation modulates the low-voltage-activated M-type potassium current (I(K,M)) in the vestibular-afferent neurons. In this work we studied the second-messenger system mediating the inhibition of I(K,M) after mAChR activation. For this, voltage and current-clamp recordings were obtained in the cultured vestibular-afferent neurons of the rat. The I(K,M) was measured during its deactivation. Response to current-pulse injection was also studied. The use of the mAChR agonist oxotremorine-M significantly reduced the amplitude of the I(K,M) and modified the discharge response to current pulses from single spike to multiple spiking, reducing the adaptation of the electrical discharge. The intracellular perfusion of the phospholipase C (PLC) inhibitor U73122 significantly attenuated the inhibitory action of the mAChR receptor agonist oxotremorine-M. Its inactive analog U73343 produced no significant action. The use of the phosphatidylinositol 4,5 bis-phosphate (PIP(2)) scavenger poly-l-lysine also led to a significant reduction of the I(K,M). Our results show that the mAChR mediated activation of PLC and subsequent PIP(2) depletion (caused by its hydrolysis), modulates the I(K,M) in the vestibular-afferent neurons, modifying their discharge response dynamics to current-pulse injection.