Mechanism and molecular basis for the sodium channel subtype specificity of µ-conopeptide CnIIIC.

ABSTRACT:

Background and purpose

Voltage-gated sodium channels (Na(V) channels) are key players in the generation and propagation of action potentials, and selective blockade of these channels is a promising strategy for clinically useful suppression of electrical activity. The conotoxin µ-CnIIIC from the cone snail Conus consors exhibits myorelaxing activity in rodents through specific blockade of skeletal muscle (Na(V) 1.4) Na(V) channels.

Experimental approach

We investigated the activity of µ-CnIIIC on human Na(V) channels and characterized its inhibitory mechanism, as well as the molecular basis, for its channel specificity.

Key results

Similar to rat paralogs, human Na(V) 1.4 and Na(V) 1.2 were potently blocked by µ-CnIIIC, the sensitivity of Na(V) 1.7 was intermediate, a

SUBMITTER: Markgraf R 

PROVIDER: S-EPMC3449262 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature