Vasopressin receptor subtypes differentially modulate calcium-activated potassium currents in the horizontal limb of the diagonal band of Broca.

摘要

The actions of vasopressin on acutely dissociated neurons within the rat horizontal limb of the diagonal band of Broca were examined using the whole-cell patch-clamp technique. Vasopressin elicited two distinct responses in 45 of 62 neurons. In one group of cells, 300 nM vasopressin decreased voltage-activated outward currents (26/45 cells) whereas in a second group, vasopressin increased outward currents (19/45 cells). The vasopressin-mediated decrease in outward currents was blocked by 1 microM Manning compound, a V1 receptor antagonist, suggesting that this response was mediated via V1 receptors. In contrast, the vasopressin-induced increase in outward current was blocked by 1 microM d(CH2)5)1,D-Ile2,Ile4,Arg8,Ala9, a V2 receptor antagonist, indicating that V2 receptor activation underlies this second response. When cells were perfused with 0 Ca2+/50 microM Cd2+, application of vasopressin did not cause any change in voltage-activated outward currents, suggesting that vasopressin modulates a calcium-dependent conductance. In the presence of 25 nM charybdotoxin, an Ic channel antagonist, vasopressin application did not influence outward currents, indicating that vasopressin modulates Ic. Currents through voltage-gated calcium channels which are responsible for activation of Ic were unaffected by vasopressin, suggesting a direct effect of vasopressin on Ic channels. These observations indicate a differential modulation of Ic channels by vasopressin via V1 and V2 receptors in the horizontal limb of the diagonal band of Broca. Our data also demonstrate the ionic mechanisms whereby vasopressin may act at V1 for V2 receptors to influence the excitability of the horizontal limb of the diagonal band of Broca neurons.