Abstract

The recent discovery of prokineticin 2 (PK2) expression in the suprachiasmatic nucleus and its receptors in critical autonomic control centers of the brain, including the subfornical organ (SFO), suggests the intriguing possibility that PK2 regulates the excitability of SFO neurons and thus influences autonomic function. Using current-clamp techniques to record from dissociated SFO neurons, we examined the effects of PK2 on the excitability of these cells. PK2 (20 nm) induced depolarizations in 40% of SFO neurons (n = 45; mean, 7.5 +/- 1.7 mV), an effect that was reversible, PK2-specific, and concentration dependent. The depolarization was accompanied by an increase in action potential frequency from 0.4 +/- 0.1 to 1.4 +/- 0.5 Hz in responding cells (n = 10). This excitatory effect appears to be, in part, attributable to a PK2-induced decrease in the delayed rectifier potassium current (I(K)). In 10 SFO neurons recorded using perforated patch voltage-clamp techniques, six demonstrated a reversible decrease in I(K) (mean decrease, 26.7 +/- 6.4%) in response to 20 nm PK2, whereas artificial CSF alone was without an effect on these currents. These data are the first to show excitatory effects of PK2 on neurons and, in addition, demonstrate that this peptide modulates voltage-activated K(+) channels. The activation of SFO neurons by PK2 illustrates a mechanism through which this peptide may exert circadian control of autonomic functions.