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

Abstract

The Na ϩ -K ϩ pump current (I p ) and the h-current (I h ) 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 ϩ -K ϩ pumps and h-channels in mesencephalic trigeminal neurons. Activation of I h leads to the generation of two types of ouabain-sensitive I p with temporal profiles similar to those of instantaneous and slow components of I h , presumably reflecting Na ϩ transients in a restricted cellular space. Moreover, the I p activated by instantaneous I h can facilitate the subsequent activation of slow I h . Such counteractive and cooperative interactions were also disclosed by replacing extracellular Na ϩ with Li ϩ , which is permeant through h-channels but does not stimulate the Na ϩ -K ϩ pump as strongly as Na ϩ ions. These observations indicate that the interactions are bidirectional and mediated by Na ϩ ions. Also after substitution of extracellular Na ϩ with Li ϩ , the tail I h was reduced markedly despite an enhancement of I h itself, attributable to a negative shift of the reversal potential for I h presumably caused by intracellular accumulation of Li ϩ ions. This suggests the presence of a microdomain where the interactions can take place. Thus, the bidirectional interactions between Na ϩ -K ϩ pumps and h-channels are likely to be mediated by Na ϩ microdomain. Consistent with these findings, hyperpolarization-activated and cyclic nucleotide-modulated subunits (HCN1/2) and the Na ϩ -K ϩ pump ␣3 isoform were colocalized in plasma membrane of mesencephalic trigeminal neurons having numerous spines.

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