Kappa-opioid receptor-mediated enhancement of the hyperpolarization-activated current (I(h)) through mobilization of intracellular calcium in rat nucleus raphe magnus.

The hyperpolarization-activated current (Ih) is important in the control of resting membrane potential, in the regulation of network firing pattern and in the modulation of presynaptic transmitter release in central neurons. Recent studies on native and cloned Ih channels have demonstrated that the Ih channel is commonly modulated by cAMP through a positive shift in its voltage dependence without a change in its maximum current. The present study demonstrates that activation of kappa-opioid receptors enhances Ih by increasing its maximum current in brainstem neurons in the nucleus raphe magnus. Agents that interfere with the release of intracellular calcium from calcium stores altered the maximum Ih and significantly attenuated the kappa-receptor-mediated enhancement of Ih. These results suggest that kappa-opioid receptors enhance the maximum Ih by mobilizing intracellular calcium from calcium stores. This provides a physiological function for kappa-receptor-stimulated calcium release and may suggest another Ih-regulating mechanism by intracellular calcium in central neurons.