THE NEWBORN RABBIT SINOATRIAL NODE EXPRESSES A NEURONAL TYPE I-LIKE NA+ CHANNEL

1. Newborn rabbit sino-atrial node (SAN) myocytes were recently found to express a tetrodotoxin (TTX)-sensitive Na+ current. We now report t hat the dose-response relation indicates that this SAN Na+ channel has unusually high TTX sensitivity, with half-maximal inhibition (26 +/- 5 nM) which is more typical of neuronal than cardiac tissue. 2. Additi onal characterization used mu-conotoxin GIIIA and Cd2+ as relatively s elective blockers of the skeletal and cardiac isoforms, respectively. mu-Conotoxin GIIIA had no effect on the current recorded from SAN myoc ytes, but the Cd2+ sensitivity was unexpectedly high for a neuronal is oform (half-maximal inhibition = 185 +/- 8 mu M). 3. Analysis of the t ime constant of inactivation did not reveal evidence of multiple inact ivation processes, with the data well fitted by a single, relatively r apid exponential (inactivation time constant = 0.58 +/- 0.03 ms at 0 m V). 4. In situ hybridization with anti-sense cDNA probes was used to t est for expression of neuronal type I, II and III Na+ channel isoforms . Myocardial cells in newborn SAN tissue exhibited clear hybridization to the type I, but not the type II or III probes. No hybridization wa s observed in adult SAN tissue with any of the three probes. 5. It is concluded that the newborn SAN expresses a neuronal type I-like Na+ ch annel isoform, and that this probably accounts for the unusual charact eristic of high sensitivity to both TTX and Cd2+.