Characterization of proton-induced currents in rat trigeminal mesencephalic nucleus neurons

Abstract

Acid-sensing ion channels (ASICs) are widely expressed in central as well as peripheral neurons. Here we have characterized the proton-induced currents in acutely isolated rat trigeminal mesencephalic nucleus (Vmes) neurons using a whole cell patch-clamp technique. In a voltage-clamp condition, the application of acid extracellular solution (≤pH 6.5) induced the inward currents in a pH-dependent manner. The proton-induced currents disappeared in the Na+-free external solution, and were concentration-dependently blocked by amiloride, a general ASIC blocker. The reversal potential of proton-induced currents was similar to the theoretical Na+ equilibrium potential, suggesting that the proton-induced currents are mainly mediated by the activation of ASICs, which are highly selective to Na+. The modulation of proton-induced currents by divalent cations and the expression patterns of ASIC transcripts using by the multi-cell RT-PCR assay suggest that Vmes neurons express functional ASIC2a and ASIC1b subunits. In a current-clamp condition, acidic pH directly depolarized the membrane potential and generated a burst of action potentials at Vmes neurons, which innervate the masseter muscle spindles. Considering that cell bodies of Vmes neurons are located within the central nervous system, ASICs expressed on Vmes neurons, by sensing peripheral and/or central acidosis, might play pivotal roles in the transduction of proprioceptive information from the masseter muscles and periodontal ligaments.