TY - JOUR
T1 - Characterization of novel sodium channels in peripheral sensory neurons
AU - Sangameswaran, L.
AU - Dietrich, P. S.
AU - Koch, B. D.
AU - Novakovic, S.
AU - Rabert, D. K.
AU - Mcgivern, J. G.
AU - Ilnicka, M.
AU - Sze, P.
AU - Tzoumaka, E.
AU - Kassotakis, L.
AU - Porreca, F.
AU - Lai, J.
AU - Eglen, R. M.
AU - Hunter, J. C.
N1 - Funding Information:
This project was financially supported by the Foundation of State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, China and The Hong Kong Polytechnic University.
PY - 1999
Y1 - 1999
N2 - Sensory neurons are known to express two different voltagegated sodium currents, one which is fast inactivating, tetrodotoxin (TTX)-sensitive and a second current which has slowinactivating kinetics and is resistant to TTX. We set out to identify and clone the voltage-gated sodium channel cDNAs expressed in rat and human dorsal root ganglia (DRG), characterize their functional properties by heterologous expression systems, map their cellular localization by in situ hybridization and immunocytochemistry, and map their chromosomal positions. The following novel sodium channel cDNAs have been isolated by homologous cloning procedures: PN1, PN3/SNS, PN4/NaCh6/scn8, PN5/NaN/SNS2, in addition to rBl, rBIII, glial sodium channel and atypical sodium channel. Of these, PN1 and PN4 are TTX-sensitive and have kinetics that are similar to the fast sodium currents recorded from the small neurons of DRG. They are expressed in both small and large neurons of the DRG and other neuronal populations within spinal cord and brain. PN3, on the other hand, has an IC50 of 100 pM for TTX and is slow inactivating, thus indicating that this cur-rent may play a significant role in high frequency burst firing that occurs in neuropathic pain. Both rPN3 and hPN3 are expressed predominantly in the small neurons of the DRG. The accumulation of PN3 immunoreactivity but not of other sodium channels at sites of injury following ligation of the sciatic nerve together with reversal of hyperalgesia and allodynia following injection of antisense oligonucleotides (i.th) are suggestive that PN3 may contribute to the abnormal processing of nociceptive information in pain states. PN5 mRNA and immunoreactivity are found predominantly in small neurons of the DRG, but within CNS, it is found localized in many different neuronal populations.
AB - Sensory neurons are known to express two different voltagegated sodium currents, one which is fast inactivating, tetrodotoxin (TTX)-sensitive and a second current which has slowinactivating kinetics and is resistant to TTX. We set out to identify and clone the voltage-gated sodium channel cDNAs expressed in rat and human dorsal root ganglia (DRG), characterize their functional properties by heterologous expression systems, map their cellular localization by in situ hybridization and immunocytochemistry, and map their chromosomal positions. The following novel sodium channel cDNAs have been isolated by homologous cloning procedures: PN1, PN3/SNS, PN4/NaCh6/scn8, PN5/NaN/SNS2, in addition to rBl, rBIII, glial sodium channel and atypical sodium channel. Of these, PN1 and PN4 are TTX-sensitive and have kinetics that are similar to the fast sodium currents recorded from the small neurons of DRG. They are expressed in both small and large neurons of the DRG and other neuronal populations within spinal cord and brain. PN3, on the other hand, has an IC50 of 100 pM for TTX and is slow inactivating, thus indicating that this cur-rent may play a significant role in high frequency burst firing that occurs in neuropathic pain. Both rPN3 and hPN3 are expressed predominantly in the small neurons of the DRG. The accumulation of PN3 immunoreactivity but not of other sodium channels at sites of injury following ligation of the sciatic nerve together with reversal of hyperalgesia and allodynia following injection of antisense oligonucleotides (i.th) are suggestive that PN3 may contribute to the abnormal processing of nociceptive information in pain states. PN5 mRNA and immunoreactivity are found predominantly in small neurons of the DRG, but within CNS, it is found localized in many different neuronal populations.
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M3 - Article
AN - SCOPUS:33748206751
SN - 0083-8969
VL - 42
SP - 145
EP - 146
JO - Proceedings of the Western Pharmacology Society
JF - Proceedings of the Western Pharmacology Society
ER -