Palmitoylcarnitine increases [Na+]i and initiates transient inward current in adult ventricular myocytes.

Abstract

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 Ca2+ ([Ca2+]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 [INa(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 < 0.01) on exposure to palmitoylcarnitine (10 microM) accompanied by the activation of INa(s); both effects were reversible. Inhibition of INa(s) by tetrodotoxin (TTX, 10 microM) 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 (Iti) and delayed afterdepolarizations (DADs). The percent inhibition (12.9 +/- 2.8%) of the Na(+)-K(+)-adenosinetriphosphatase pump activity by palmitoylcarnitine (10 microM) was much smaller than that induced by ouabain (10 microM, 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 INa(s) leading to an increase in [Na+]i, which elicits an increase in [Ca2+]i probably via the Na+/Ca2+ exchanger, thereby leading to the development of Iti and DADs.

• Authors: J Wu, P B Corr
• Journal: The American journal of physiology (Am J Physiol) Vol. 268 Issue 6 Pt 2 Pg. H2405-17 (Jun 1995) ISSN: 0002-9513 [Print] United States
• PMID: 7611493 (Publication Type: Journal Article)

Chemical References

• Palmitoylcarnitine
• Tetrodotoxin
• Egtazic Acid
• Ouabain
• nickel chloride
• Nickel
• Sodium
• Sodium-Potassium-Exchanging ATPase
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Egtazic Acid (pharmacology)
• Electrophysiology (methods)
• Female
• Heart (drug effects, physiology)
• Heart Ventricles
• In Vitro Techniques
• Male
• Myocardium (metabolism)
• Nickel (pharmacology)
• Ouabain (pharmacology)
• Palmitoylcarnitine (pharmacology)
• Rabbits
• Sarcolemma (enzymology)
• Sodium (metabolism)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Tetrodotoxin (pharmacology)
• Time Factors