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

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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 ofIhleads to the generation of two types of ouabain-sensitiveIpwith temporal profiles similar to those of instantaneous and slow components ofIh, presumably reflecting Na+transients in a restricted cellular space. Moreover, theIpactivated by instantaneousIhcan facilitate the subsequent activation of slowIh. 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 tailIhwas reduced markedly despite an enhancement ofIhitself, attributable to a negative shift of the reversal potential forIhpresumably 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+pumpα3 isoform were colocalized in plasma membrane of mesencephalic trigeminal neurons having numerous spines.