Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by µ-conotoxins.
Br J Pharmacol
; 169(1): 102-14, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23351163
ABSTRACT
BACKGROUND AND PURPOSE:
Adult rat dorsal root ganglion (DRG) neurons normally express transcripts for five isoforms of the α-subunit of voltage-gated sodium channels NaV 1.1, 1.6, 1.7, 1.8 and 1.9. Tetrodotoxin (TTX) readily blocks all but NaV 1.8 and 1.9, and pharmacological agents that discriminate among the TTX-sensitive NaV 1-isoforms are scarce. Recently, we used the activity profile of a panel of µ-conotoxins in blocking cloned rodent NaV 1-isoforms expressed in Xenopus laevis oocytes to conclude that action potentials of A- and C-fibres in rat sciatic nerve were, respectively, mediated primarily by NaV 1.6 and NaV 1.7. EXPERIMENTALAPPROACH:
We used three µ-conotoxins, µ-TIIIA, µ-PIIIA and µ-SmIIIA, applied individually and in combinations, to pharmacologically differentiate the TTX-sensitive INa of voltage-clamped neurons acutely dissociated from adult rat DRG. We examined only small and large neurons whose respective INa were >50% and >80% TTX-sensitive. KEYRESULTS:
In both small and large neurons, the ability of the toxins to block TTX-sensitive INa was µ-TIIIA < µ-PIIIA < µ-SmIIIA, with the latter blocking â³90%. Comparison of the toxin-susceptibility profiles of the neuronal INa with recently acquired profiles of rat NaV 1-isoforms, co-expressed with various NaV ß-subunits in X. laevis oocytes, were consistent NaV 1.1, 1.6 and 1.7 could account for all of the TTX-sensitive INa , with NaV 1.1 < NaV 1.6 < NaV 1.7 for small neurons and NaV 1.7 < NaV 1.1 < NaV 1.6 for large neurons. CONCLUSIONS AND IMPLICATIONS Combinations of µ-conotoxins can be used to determine the probable NaV 1-isoforms underlying the INa in DRG neurons. Preliminary experiments with sympathetic neurons suggest that this approach is extendable to other neurons.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tetrodotoxina
/
Conotoxinas
/
Gânglios Espinais
/
Neurônios
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article