Sodium-Coupled Neutral Amino Acid Cotransporter Inhibited by the Volatile Anesthetic, Halothane, in Megakaryocytes

Hitoshi Shimada, Yukinari Tomita, Gen Inooka, Yoshio Maruyama

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

We have studied the effects of halothane, a popular volatile anesthetic, on Na+-coupled L-alanine cotransporters using rat bone marrow megakaryocytes subjected to patch-clamp whole-cell recordings. L-Alanine applied externally induced an immediate current response which was abolished by the elimination of external NaCl. The optical isomer, D-alanine, induced no such response. A ligand probe for the Na+-dependent amino-acid cotransporter (A-system), 2-methylaminoisobutyrate, induced a response comparable to that of L-alanine. The response was fitted by a Michaelis-Menten equation with a Km of 2.5 and 58.5mM for L-alanine (with 120 mM Na+) and external Na+ (with 10 mM L-alanine), respectively. The volatile anesthetic, halothane, acutely and reversibly inhibited the inward current responsible for the Na+-coupled L-alanine cotransporter. Complete inhibition was attained at 1 mM, and 50%-inhibition at 0.35 mM. Halothane in a clinically relevant concentration reduced nutrient uptake via the cotransporter A-system. The sensitivity of the A-system to halothane is comparable to or greater than that of Na+/K+/Cl- cotransporter, sodium/proton exchange, stimulus-secretion coupling, and of many ion channels in nerve cells.

Original languageEnglish
Pages (from-to)165-176
Number of pages12
JournalJapanese Journal of Physiology
Volume45
Issue number1
DOIs
Publication statusPublished - 1995

Keywords

  • A-system
  • alanine cotransport
  • halothane
  • megakaryocytes
  • sodium current

ASJC Scopus subject areas

  • Physiology

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