The physiology and pharmacology of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons.

摘要

Tetrodotoxin (TTX) has been used as a classic tool in electrophysiological studies, as it specifically blocks transient voltage-dependent sodium current in a variety of preparations. Sodium channels resistant to TTX block have been reported in amphibian, reptilian, and mammalian nervous systems. The goal of this research was to characterize these channels in the mammalian nervous system.;TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) sodium channel currents were analyzed in acutely dissociated dorsal root ganglion (DRG) neurons isolated from 3-12 day old and adult rats. Currents were recorded using whole-cell and single-channel configurations of the patch clamp technique. These two current types were expressed as a function of rat age and neuron diameter. TTX-R and TTX-S currents differed markedly in their activation and inactivation kinetics. At the single channel level, two distinct amplitudes and conductances were observed which, based upon biophysical characteristics and TTX block, were identified as TTX-S and TTX-R channels.;The pharmacological analyses of these sodium channel subtypes utilized various neurotoxins which bind to specific amino acid components in the brain sodium channel protein. TTX-S currents were blocked by nanomolar concentrations of TTX and saxitoxin, whereas TTX-R currents were still observed in 100 micromolar concentrations of these toxins. The hydrophobic toxins aconitine and ;The physiological and pharmacological properties of the TTX-R and TTX-S channels in this preparation raise intriguing questions as to their roles in CNS development, function, and drug interactions.