Roles of PLCβ, PIP2 , and GIRK channels in arginine vasopressin-elicited excitation of CA1 pyramidal neurons.

Arginine vasopressin (AVP) is a hormone exerting vasoconstrictive and antidiuretic action in the periphery and serves as a neuromodulator in the brain. Although the hippocampus receives vasopressinergic innervation and AVP has been shown to facilitate the excitability of CA1 pyramidal neurons, the involved ionic and signaling mechanisms have not been determined. Here we found that AVP excited CA1 pyramidal neurons by activation of V1a receptors. Functions of G proteins and phospholipase Cβ (PLCβ) were required for AVP-elicited excitation of CA1 pyramidal neurons, whereas intracellular Ca2+ release and protein kinase C were unnecessary. PLCβ-mediated depletion of phosphatidylinositol 4,5-bisphosphate (PIP2 ) was required for AVP-elicited excitation of CA1 pyramidal neurons. AVP augmented the input resistance and increased the time constants of CA1 pyramidal neurons. AVP induced an inward current in K+ -containing intracellular solution, whereas no inward currents were observed with Cs+ -containing intracellular solution. AVP-sensitive currents showed inward rectification with a reversal potential close to the K+ reversal potential, suggesting the involvement of inwardly rectifying K+ channels. AVP-induced currents were sensitive to the micromolar concentration of Ba2+ and tertiapin-Q, whereas application of ML 133, a selective Kir2 channel blocker had no effects, suggesting that AVP excited CA1 pyramidal neurons by depressing G protein-gated inwardly rectifying K+ channels. Activation of V1a receptors in the CA1 region facilitated glutamatergic transmission onto subicular pyramidal neurons, suggesting that AVP modulates network activity in the brain. Our results may provide one of the cellular and molecular mechanisms to explain the in vivo physiological functions of AVP.