Identification and characterization of a subset of mouse sensory neurons that express acid-sensing ion channel 3.
Acid-sensing ion channel 3 (ASIC3) is the most sensitive acid sensor in sensory neurons that innervate into skin, muscle, heart, and visceral tissues. ASIC3 is involved in ischemia sensing, nociception, mechanosensation, and hearing, but how ASIC3-expressing neurons differ in their firing properties is still unknown. We hypothesized that ASIC3-expressing neurons have specialized firing properties, which, coupled with the heterogeneity of acid-sensing properties, accounts for various physiological roles. Here, we successfully identified ASIC3-expressing lumbar dorsal root ganglion (DRG) neurons whose transient proton-gated currents were blocked by salicylic acid (SA). The salicylic acid-sensitive (SAS) neurons did not exist in DRG neurons of mice lacking ASIC3. SAS neurons expressed distinct electrophysiological properties as compared with other DRG neurons. Especially, SAS neurons fired action potentials (APs) with large overshoot and long afterhyperpolarization duration, which suggests that they belong to nociceptors. SAS neurons also exhibited multiple nociceptor markers such as capsaicin response (38%), action potential (AP) with inflection (35%), or tetrodotoxin resistance (31%). Only in SAS neurons but not other DRG neurons was afterhyperpolarization duration correlated with resting membrane potential and AP duration. Our studies reveal a unique feature of ASIC3-expressing DRG neurons and a basis for their heterogeneous functions.
Lin
Y-W
YW
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China.
Min
M-Y
MY
Lin
C-C
CC
Chen
W-N
WN
Wu
W-L
WL
Yu
H-M
HM
Chen
C-C
CC
D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011522:Protons; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020156:Salicylic Acid / Q000633:toxicity; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics*; D050916:TRPV Cation Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D011522:Protons; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013779:Tetrodotoxin; D020156:Salicylic Acid