Sodium-activated potassium current is activated by the acid sensing ionic channels mediated Na+ influx in afferent vestibular neurons

Abstract

Vestibular afferent neurons (VANs) dynamics encode linear and angular acceleration within their firing patterns which are heavily influenced by the K+ conductance expressed by vestibular neurons. In previous work we shown that the two sodium activated potassium channels (KNa) subunits (Slack and Slick) are expressed in the VANs (Cervantes et al., 2013). Activation of KNa depends of the intracellular Na+. It was shown that Na+ increase caused by activation of sodium channels during the action potential is sufficient to activate the KNa. Thence, we asked whether the large Na+ influx caused by acid sensing ion channels (ASIC) will also activate the KNa. To answer this question ionic currents in isolated VANs were recorded by whole cell voltage clamp technique. Confocal microscopy analysis of colocalization using anti ASIC1 and anti Slack or Slick antibodies were also performed. In the voltage clamp to activate the ASIC current an acid pulse of pH 6.1 (5 s) was used, according to Mercado et al., 2006. We found that in 19 % of the cells (n = 26) the typical inward ASIC current was followed by an outward current at the end of the acidic pulse. Given that it has been shown that Li+ permeate through the ASICs but does not activates the KNa current. In our experiments the substitution of Li+ for Na+ in the extracellular solution (pH 7.4 and 6.1) did not modify the peak, sustained current, time course or desensitization of the acid gated inward current (P > 0.05, n =5), however Li+ significantly decreased the outward current which follows the ASIC activation 39 ± 12 % (P < 0.05, n = 5). The use of fluorescence antibodies shown that ASIC1 and Slick or Slack signals colocalize in the vestibular ganglion neurons and in the vestibular sensory epithelium. These results suggest that Na+ influx through the ASICs may activate the KNa current producing an outward current at the end of the acid gated current.