Sodium-coupled neutral amino acid cotransporter inhibited by the volatile anesthetic, halothane, in megakaryocytes.
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 58.5 mM 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.
Shimada
H
H
Department of Anesthesiology, Gumma University School of Medicine, Maebashi, Japan.
Tomita
Y
Y
Inooka
G
G
Maruyama
Y
Y
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D027981:Symporters
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D027981:Symporters; C052168:sodium-alanine cotransporter; D012964:Sodium; D006221:Halothane