Human, Rodent, and Canine Pancreatic β-cells Express a Sodium Channel α₁-Subunit Related to a Fetal Brain Isoform

Voltage-dependent, tetrodotoxin-sensitive Na⁺ currents have been identified by the patch-clamp technique in rodent, canine, and human pancreatic β-cells, but their exact role in insulin secretion remains uncertain. Misler et al. recently reviewed data showing that human and rat β-cell action potentials differ, in that trains of Na⁺-dependent action potentials are seen in human (and canine) cells, but the vast majority of rat β-cell Na⁺ channels are inactivated. We have now identified Na⁺ channel α₁-subunit mRNAs expressed in normal adult human, canine, and rat islets, and two insulinoma cell lines, by mRNA amplification (reverse transcription followed by polymerase chain reaction). cDNA sequencing showed that all amplified human islet products and the majority of rodent islet cDNAs are most closely related to the rat brain III α₁-subunit isoform, previously found to be expressed primarily in fetal rat brain. Canine islets expressed both brain II and brain III isoforms. Reverse transcription followed by polymerase chain reaction experiments with hamster and mouse insulinoma cell lines also showed expression of the message related to the rat brain III isoform. In situ hybridization of human pancreas sections using a partial human Na⁺ channel III cDNA probe showed the message to be expressed in the majority of islet cells, and not in the acinar tissue, confirming its presence in pancreatic β-cells. Thus, the predominant Na⁺ channel α₁-subunit gene expressed in human and rat insulin secreting cells is most highly related to a fetal rat brain isoform, despite the differences in the role of this channel in the β-cell action potentials of these two species.