Nicotinic acetylcholine receptors in dorsal root ganglion neurons include the α6β4* subtype.
The α6-containing nicotinic acetylcholine receptors (nAChRs) have recently been implicated in diseases of the central nervous system (CNS), including Parkinson's disease and substance abuse. In contrast, little is known about the role of α6* nAChRs in the peripheral nervous system (where the asterisk denotes the possible presence of additional subunits). Dorsal root ganglia (DRG) neurons are known to express nAChRs with a pharmacology consistent with an α7, α3β4*, and α4β2* composition. Here we present evidence that DRG neurons also express α6* nAChRs. We used RT-PCR to show the presence of α6 subunit transcripts and patch-clamp electrophysiology together with subtype-selective α-conotoxins to pharmacologically characterize the nAChRs in rat DRG neurons. α-Conotoxin BuIA (500 nM) blocked acetylcholine-gated currents (I(ACh)) by 90.3 ± 3.0%; the recovery from blockade was very slow, indicating a predominance of α(x)β4* nAChRs. Perfusion with either 300 nM BuIA[T5A;P6O] or 200 nM MII[E11A], α-conotoxins that target the α6β4* subtype, blocked I(ACh) by 49.3 ± 5 and 46.7 ± 8%, respectively. In these neurons, I(ACh) was relatively insensitive to 200 nM ArIB[V11L;V16D] (9.4±2.0% blockade) or 500 nM PnIA (23.0±4% blockade), α-conotoxins that target α7 and α3β2*/α6β2* nAChRs, respectively. We conclude that α6β4* nAChRs are among the subtypes expressed by DRG, and to our knowledge, this is the first demonstration of α6β4* in neurons outside the CNS.
Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, Utah, USA.
Arik J
AJ
Hone
Erin L
EL
Meyer
Melissa
M
McIntyre
J Michael
JM
McIntosh
D000818:Animals; D020916:Conotoxins / Q000494:pharmacology; D055724:Electrophysiological Phenomena; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000145:classification / Q000378:metabolism*
D020916:Conotoxins; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C515221:alpha-conotoxin BuIA, Conus bullatus; C532888:alpha-conotoxin IB, Leu(11), Asp(16)-; C104518:nicotinic receptor alpha6