Acid sensing ion channels in dorsal spinal cord neurons.
Acid-sensing ion channels (ASICs) are broadly expressed in the CNS, including the spinal cord. However, very little is known about the properties of ASICs in spinal cord neurons compared with brain. We show here that ASIC1a and ASIC2a are the most abundant ASICs in mouse adult spinal cord and are coexpressed by most neurons throughout all the laminas. ASIC currents in cultured embryonic day 14 mouse dorsal spinal neurons mainly flow through homomeric ASIC1a (34% of neurons) and heteromeric ASIC1a plus 2a channels at a ratio of 2:1 (83% of neurons). ASIC2b only has a minor contribution to these currents. The two channel subtypes show different active pH ranges and different inactivation and reactivation kinetics supporting complementary functional properties. One striking property of native dorsal spinal neuron currents and recombinant currents is the pH dependence of the reactivation process. A light sustained acidosis induces a threefold slow-down of the homomeric ASIC1a (from pH 7.4 to pH 7.3) and heteromeric ASIC1a plus 2a (from pH 7.4 to pH 7.2) current reactivation (T(0.5) increasing from 5.77 to 16.84 s and from 0.98 to 3.2 s, respectively), whereas a larger acidosis to pH 6.6 induces a 32-fold slow-down of the ASIC1a plus 2a current reactivation (T(0.5) values increasing to 31.30 s). The pH dependence of ASIC channel reactivation is likely to modulate neuronal excitability associated with repetitive firing in response to extracellular pH oscillations, which can be induced, for example, by intense synaptic activity of central neurons.
Baron
Anne
A
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université de Nice Sophia-Antipolis, Unité Mixte de Recherche 6097, Sophia Antipolis, 06560 Valbonne, France. baron@ipmc.cnrs.fr
Voilley
Nicolas
N
Lazdunski
Michel
M
Lingueglia
Eric
E
D062565:Acid Sensing Ion Channels; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D015222:Sodium Channels / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism*
C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels