Inhibition of GluR Current in Microvilli of Sensory Neurons via Na⁺-Microdomain Coupling Among GluR, HCN Channel, and Na⁺/K⁺ Pump.

Glutamatergic dendritic EPSPs evoked in cortical pyramidal neurons are depressed by activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels expressed in dendritic spines. This depression has been attributed to shunting effects of HCN current (I_h) on input resistance or I_h deactivation. Primary sensory neurons in the rat mesencephalic trigeminal nucleus (MTN) have the somata covered by spine-like microvilli that express HCN channels. In rat MTN neurons, we demonstrated that I_h enhancement apparently diminished the glutamate receptor (GluR) current (I_GluR) evoked by puff application of glutamate/AMPA and enhanced a transient outward current following I_GluR (OT-I_GluR). This suggests that some outward current opposes inward I_GluR. The I_GluR inhibition displayed a U-shaped voltage-dependence with a minimal inhibition around the resting membrane potential, suggesting that simple shunting effects or deactivation of I_h cannot explain the U-shaped voltage-dependence. Confocal imaging of Na⁺ revealed that GluR activation caused an accumulation of Na⁺ in the microvilli, which can cause a negative shift of the reversal potential for I_h (E_h). Taken together, it was suggested that I_GluR evoked in MTN neurons is opposed by a transient decrease or increase in standing inward or outward I_h, respectively, both of which can be caused by negative shifts of E_h, as consistent with the U-shaped voltage-dependence of the I_GluR inhibition and the OT-I_GluR generation. An electron-microscopic immunohistochemical study revealed the colocalization of HCN channels and glutamatergic synapses in microvilli of MTN neurons, which would provide a morphological basis for the functional interaction between HCN and GluR channels. Mathematical modeling eliminated the possibilities of the involvements of I_h deactivation and/or shunting effect and supported the negative shift of E_h which causes the U-shaped voltage-dependent inhibition of I_GluR.

Duke Scholars

Author Seog Oh Physics