Activation of V(1a) vasopressin receptors excite subicular pyramidal neurons by activating TRPV1 and depressing GIRK channels.

Arginine vasopressin (AVP) is a nonapeptide that serves as a neuromodulator in the brain and a hormone in the periphery that regulates water homeostasis and vasoconstriction. The subiculum is the major output region of the hippocampus and an integral component in the networks that processes sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whereas the subiculum expresses high densities of AVP-binding sites and AVP has been shown to increase the synaptic excitability of subicular pyramidal neurons, the underlying cellular and molecular mechanisms have not been determined. We found that activation of V(1a) receptors increased the excitability of subicular pyramidal neurons via activation of TRPV1 channels and depression of the GIRK channels. V(1a) receptor-induced excitation of subicular pyramidal neurons required the function of phospholipase Cβ, but was independent of intracellular Ca(2+) release. Protein kinase C was responsible for AVP-mediated depression of GIRK channels, whereas degradation of phosphatidylinositol 4,5-bisphosphate was involved in V(1a) receptor-elicited activation of TRPV1 channels. Our results may provide one of the cellular and molecular mechanisms to explain the physiological functions of AVP in the brain.