Palmitoylcarnitine increases [Na+]i and initiates transient inward current in adult ventricular myocytes
Wu, J.; Corr, P.B.
American Journal of Physiology 268(6 Pt 2): H2405-H2417
1995
ISSN/ISBN: 0002-9513 PMID: 7611493 Document Number: 447315
This study was performed to determine whether long-chain acylcarnitines, specifically palmitoylcarnitine, could account for the increase in intracellular Na+ ((Na+)-i) during ischemia eliciting a secondary increase in intracellular Ca-2+ ((Ca-2+)-i). Accordingly, whole cell voltage-clamp procedures and Na+-sensitive electrode recordings were employed simultaneously in isolated adult rabbit ventricular myocytes to assess the relationship between activation of a slow-inactivating Na+ current (I-Na(s)) and a potential increase in (Na+)-i. The (Na+)-i increased progressively from 8.4 +- 1.2 to 22.5 +- 1.8 mM (n = 8, P lt 0.01) on exposure to palmitoylcarnitine (10 mu-M) accompanied by the activation of I-Na(s); both effects were reversible. Inhibition of I-Na(s) by tetrodotoxin (TTX, 10 mu-M) inhibited the increase in (Na+)-i. Increasing (Na+)-i to 20 mM without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to mimic effects measured with palmitoylcarnitine consistently elicited the transient inward current (I-ti) and delayed after depolarizations (DADs). The percent inhibition (12.9 +- 2.8%) of the Na+-K+-adenosine-triphosphatase pump activity by palmitoylcarnitine (10 mu-M) was much smaller than that induced by ouabain (10 mu-M, 90.5 +- 2.5%), suggesting that this modest effect of palmitoylcarnitine on the pump is unlikely to account for the increase in (Na+)-i induced by palmitoylcarnitine. Thus palmitoylcarnitine induces the I-Na(s) leading to an increase in (Na+)-i, which elicits an increase in (Ca-2+)-i probably via the Na+/Ca-2+ exchanger, thereby leading to the development of I-ti and DADs.