Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome.

ABSTRACT:

Rationale

Familial sick sinus syndrome (SSS) has been linked to loss-of-function mutations of the SCN5A gene, which result in decreased inward Na(+) current, I(Na). However, the functional role of I(Na) in cardiac pacemaking is controversial, and mechanistic links between mutations and sinus node dysfunction in SSS are unclear.

Objective

To determine mechanisms by which the SCN5A mutations impair cardiac pacemaking.

Methods and results

Action potential (AP) models for rabbit sinoatrial node (SAN) cells were modified to incorporate experimentally reported I(Na) changes induced by 2 groups of SCN5A gene mutations (affecting the activation and inactivation of I(Na), respectively). The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-

SUBMITTER: Butters TD 

PROVIDER: S-EPMC2901593 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature