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Mechanisms of Sodium Transport at the Blood‐Brain Barrier Studied with In Situ Perfusion of Rat Brain
Author(s) -
Ennis Steven R.,
Ren Xiaodan,
Betz A. Lorris
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66020756.x
Subject(s) - chemistry , sodium , bumetanide , paracellular transport , blood–brain barrier , symporter , transcellular , sodium channel , amiloride , biophysics , biochemistry , cotransporter , endocrinology , transporter , membrane , permeability (electromagnetism) , central nervous system , medicine , organic chemistry , biology , gene
The mechanism of unidirectional transport of sodium from blood to brain in pentobarbital‐anesthetized rats was examined using in situ perfusion. Sodium transport followed Michaelis‐Menten saturation kinetics with a V max of 50.1 nmol/g/min and a K m of 17.7 m M in the left frontal cortex. The kinetic analysis indicated that, at a physiologic sodium concentration, ∼26% of sodium transport at the blood‐brain barrier (BBB) was carrier mediated. Dimethylamiloride (25 µ M ), an inhibitor of Na + /H + exchange, reduced sodium transport by 28%, whereas phenamil (25 µ M ), a sodium channel inhibitor, reduced the transfer constant for sodium by 22%. Bumetanide (250 µ M ) and hydrochlorothiazide (1.5 m M ), inhibitors of Na + ‐K + ‐2Cl − /NaCl symport, were ineffective in reducing blood to brain sodium transport. Acetazolamide (0.25 m M ), an inhibitor of carbonic anhydrase, did not change sodium transport at the BBB. Finally, a perfusate pH of 7.0 or 7.8 or a perfusate P co 2 of 86 mm Hg failed to change sodium transport. These results indicate that 50% of transcellular transport of sodium from blood to brain occurs through Na + /H + exchange and a sodium channel in the luminal membrane of the BBB. We propose that the sodium transport systems at the luminal membrane of the BBB, in conjunction with Cl − /HCO 3 − exchange, lead to net NaCl secretion and obligate water transport into the brain.