title: Acid modulation of tetrodotoxin-sensitive Na+channels in large-sized trigeminal ganglion neurons.
abstract: Voltage-gated Na+channels in primary afferent neurons can be divided into tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na+channels. Although previous studies have shown the acid modulation of TTX-R Na+channels, the effect of acidic pH on tetrodotoxin-sensitive (TTX-S) Na+channels is still unknown. Here we report the effect of acidic pH on TTX-S Na+channels expressed in large-sized trigeminal ganglion (TG) neurons using a whole-cell patch clamp technique. The application of acidic extracellular solution decreased the peak amplitude of TTX-S currents (INa) in a pH-dependent manner, but weak acid (≥pH 6.0) had no inhibitory effect on TTX-S INa. Acidic pH (pH 6.0) shifted both the activation and steady-state fast inactivation relationships of TTX-S Na+channels toward depolarized potentials. However, acidic pH (pH 6.0) had no effect on use-dependent inhibition in response to high-frequency stimuli, development of inactivation, and accelerated the recovery from inactivation of TTX-S Na+channels, suggesting that TTX-S Na+channels in large-sized TG neurons are less sensitive to acidic pH. Given that voltage-gated Na+channels play a pivotal role in the generation and conduction of action potentials in neural tissues, the insensitivity of TTX-S Na+channels expressed in large-sized TG neurons to acidic pH would ensure transmission of innocuous tactile sensation from orofacial regions at acidic pH conditions.
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors.forename: Michiko
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors.forename: Do-Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea. Electronic address: jis7619@knu.ac.kr.
authors.forename: Il-Sung
authors.initials: IS
authors.lastname: Jang
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000143:Acids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D005110:Extracellular Space / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000143:Acids; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin
keywords: Acidosis; Aβ-type afferents; Patch clamp; TTX-S Na(+) channels; Trigeminal ganglia