Pathological enhancement of late @entity4024 current (INa) can potentially modify intracellular ion homeostasis and contribute to @entity299 . We tested the hypothesis that modulation of late INa can be a source of intracellular @entity4024 ([ @entity4024 ]i) overload. Late INa was enhanced by exposing @entity95 ventricular myocytes to Anemonia sulcata toxin II (ATX-II) and measured using whole cell patch-clamp technique. [Na(+)]i was determined with fluorescent dye Asante NaTRIUM Green-2 AM. Pacing-induced changes in the dye fluorescence measured at 37  C were more pronounced in ATX-II-treated cells than in control (dye washout prevented calibration). At 22-24  C, resting [ @entity4024 ]i was 6.6    0.8 mM. Treatment with 5 nM ATX-II increased late INa 8.7-fold. [ @entity4024 ]i measured after 2 min of electrical stimulation (1 Hz) was 10.8    1.5 mM and 22.1    1.6 mM (P < 0.001) in the absence and presence of 5 nM ATX-II, respectively. Inhibition of late INa with @entity69195 (1  M) prevented @entity4024 i accumulation. A strong positive correlation was observed between the late INa and the pacing-induced increase of [Na(+)]i (R(2) = 0.88) and between the rise in [ @entity4024 ]i and the increases in cytosolic @entity141 (R(2) = 0.96). ATX-II, @entity1022 , or @entity69195 did not affect [ @entity4024 ]i in quiescent myocytes suggesting that late INa was solely responsible for triggering the ATX-II effect on [ @entity4024 ]i. Experiments with @entity1706 and @entity9690 indicate that prolongation of the action potential contributes to as much as 50% of the [ @entity4024 ]i overload associated with the increase in late INa caused by ATX-II. Enhancement of late INa can cause intracellular @entity4024 overload in ventricular myocytes.

Contribution of the late sodium current to intracellular sodium and calcium overload in XXXX ventricular myocytes treated by anemone toxin.

@entity4024 :: ('D012964', 'Chemical') :: ['Na(+)'] @entity69195 :: ('MESH:C578456', 'Chemical') :: ['GS-967'] @entity1022 :: ('MESH:D013779', 'Chemical') :: ['tetrodotoxin'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity9690 :: ('MESH:C063968', 'Chemical') :: ['E4031'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac dysfunction'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity1706 :: ('MESH:D020110', 'Chemical') :: ['pinacidil']
@entity95 :: (9986,Species) :: ['rabbit']
