Bidirectional Interactions between H-Channels and Na+-K + Pumps in Mesencephalic Trigeminal Neurons

Abstract

The Na+-K+ pump current (Ip) and the h-current (Ih) flowing through hyperpolarization-activated channels (h-channels) participate in generating the resting potential. These two currents are thought to be produced independently. We show here bidirectional interactions between Na+-K+ pumps and h-channels in mesencephalic trigeminal neurons. Activation of Ih leads to the generation of two types of ouabain-sensitive Ip with temporal profiles similar to those of instantaneous and slow components of I h, presumably reflecting Na+ transients in a restricted cellular space. Moreover, the Ip activated by instantaneous I h can facilitate the subsequent activation of slow Ih. Such counteractive and cooperative interactions were also disclosed by replacing extracellular Na+ with Li+, which is permeant through h-channels but does not stimulate the Na+-K+ pump as strongly as Na+ ions. These observations indicate that the interactions are bidirectional and mediated by Na+ ions. Also after substitution of extracellular Na+ with Li+, the tail Ih was reduced markedly despite an enhancement of Ih itself, attributable to a negative shift of the reversal potential for I h presumably caused by intracellular accumulation of Li+ ions. This suggests the presence of a microdomain where the interactions can take place. Thus, the bidirectional interactions between Na+-K + pumps and h-channels are likely to be mediated by Na+ microdomain. Consistent with these findings, hyperpolarization-activated and cyclic nucleotide-modulated subunits (HCN1/2) and the Na+-K + pump α3 isoform were colocalized in plasma membrane of mesencephalic trigeminal neurons having numerous spines.