Reactive oxygen species originating from mitochondria regulate the cardiac sodium channel.

ABSTRACT:

Rationale

Pyridine nucleotides regulate the cardiac Na(+) current (I(Na)) through generation of reactive oxygen species (ROS).

Objective

We investigated the source of ROS induced by elevated NADH.

Methods and results

In human embryonic kidney (HEK) cells stably expressing the cardiac Na(+) channel, the decrease of I(Na) (52±9%; P<0.01) induced by cytosolic NADH application (100 μmol/L) was reversed by mitoTEMPO, rotenone, malonate, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), PK11195, and 4'-chlorodiazepam, a specific scavenger of mitochondrial superoxide and inhibitors of the mitochondrial complex I, complex II, voltage-dependent anion channels, and benzodiazepine receptor, respectively. Anti-mycin A (20 μmol/L), a complex III inhibitor known to generat

SUBMITTER: Liu M 

PROVIDER: S-EPMC2955818 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature