Activation of outward current by pituitary adenylate cyclase activating polypeptide in mouse microglial cells

In order to investigate the interaction between the nervous and immune systems, we have analyzed the effect of one of the neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP), on microglia cells by the patch-clamp method. Puff application of PACAP38 onto mouse microglial cells induced an outward current in a dose-dependent manner. Reversal potentials of the outward current were dependent on external K+ concentrations ([K+]0) and independent of [Cl-]0. Ion channel blockers of potassium currents, quinine (1 mM), tetraethylammonium (TEA, 20 mM) and 4-aminopyridine (4-AP, 5 mM), suppressed the outward current with a potency order of quinine>TEA>4-AP. PACAP27 also induced outward current less effectively than PACAP38. A fragment of PACAP38 [PACAP(6-38)], known as an inhibitor for PACAP38, suppressed the outward current. These data suggest that PACAP38 activates a quinine-sensitive K+ outward current and modulates activities in microglia. They indicate that the immune system in the brain can be modulated by neurotransmitters, the mediators of neurons.