J Physiol Volume 586, Number 16, 3917-3926, August 15, 2008 DOI: 10.1113/jphysiol.2008.156299
Role of the amino and carboxy termini in isoform-specific sodium channel variation
Annie Lee1 and
Alan L. Goldin1
1 Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA
Nav1.2 and Nav1.6 are two voltage-gated sodium channel isoforms found in adult CNS neurons. These isoforms differ in their electrophysiological properties, even though the major regions that are known to be involved in channel activation and inactivation are conserved between them. To determine if the terminal domains of these channels contributed to their activation and fast inactivation differences, we constructed chimeras between the two isoforms and characterized their electrophysiological properties. Exchanging the N-terminal 205 amino acids of Nav1.6 and the corresponding 202 amino acids of Nav1.2 completely swapped the V_1/2 of steady-state activation between the Nav1.2 and Nav1.6 channels in an isoform-specific manner. Exchanging the C-terminal 436 amino acids of Nav1.6 and the corresponding region of Nav1.2 altered the voltage dependence and kinetics of steady-state inactivation, but the changes did not reflect a direct transfer of inactivation properties between the two isoforms. Finally, the N- and C-terminal domains from Nav1.6 demonstrated functional cooperation. These results suggest that the terminal sequences of the sodium channel are important for isoform-specific differences between the channels.
(Received 5 May 2008;
accepted after revision 18 June 2008;
first published online 19 June 2008)
Corresponding author A. L. Goldin: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA. Email: agoldin{at}uci.edu
Copyright © 2008 The Physiological Society.
