Molecular cloning of a putative tetrodotoxin-resistant sodium channel from dog nodose ganglion neurons

Voltage-gated tetrodotoxin (TTX)-resistant sodium channels present in primary sensory neurons may be responsible for the excitability of nociceptors, and may underlie pain and tenderness associated with tissue injury and inflammation. Here, we report the cloning of a putative sodium channel (NaNG) from dog nodose ganglia. The sequence of the full-length cDNA predicts an open reading frame of 5886 nucleotides encoding a protein of 1962 amino acids. The predicted protein shows 82.3% identity with the recently discovered TTX-resistant sodium channel (SNS/PN3). In the TTX-binding site, a serine appears as in TTX-resistant SNS/PN3, instead of Cys (as in TTX-insensitive cardiac channels) and Tyr/Phe (as in TTX-sensitive sodium channels). Coupled transcription and translation of full-length cDNA produced a 220-kDa protein; based on Northern blot and RT-PCR analysis, its expression is restricted to nodose ganglia, and not present in cortex, hippocampus, cerebellum, liver, heart or skeletal muscle. We propose that NaNG might be a new member of the TTX-resistant sodium channel family expressed in sensory neurons.