Sodium/proton antiporters in the mitochondrial inner membrane.
The two mitochondrial Na+/H+ antiporters differ in several important respects, and the most physiologically significant of these may be their differences in regulation. The Mg2+-dependent Na+/H+ antiporter controls mitochondrial volume in a dangerous, high-K+ environment. To play this vital role, this porter must always lie poised far from K+/H+ equilibrium; i.e., it must be under dynamic regulation, as proposed in the Mg2+ carrier-brake hypothesis (7). Being regulated, it is not necessary for this antiporter to be cation-selective, since all electroneutral cation movements will be followed by redistributions of anions and water. On the other hand, there is no indication at present that the Mg2+-independent Na+/H+ antiporter is regulated. This transporter is therefore required to exhibit high discrimination against K+ in order to prevent the collapse of matrix volume dueto uncontrolled loss of K+ salts and water (4). Do the properties of the mitochondrial Na+/H+ antiporters help us in any way to understand the plasmalemmal Na+/H+ antiporters? I believe they do, if we allow that there are a limited number of ways in which nature constructs such porters. The difference in cation selectivities very likely reflects a fundamental structural difference between the two mitochondrial antiporters, and this difference appears to be mirrored in two types of plasmalemmal Na+/H+ antiporters. Thus, the Mg2+-independent Na+/H+ antiporter resembles the renal tubular Na+/H+ antiporter in its discrimination against K+ and its competitive inhibition by Li+. On the other hand, the Mg2+-dependent Na+/H+ antiporter resembles a cardiac sarcolemmal Na+/H+ antiporter which transports all alkali cations, including Na+ and K+, and which is inhibited by DCCD and amphiphilic amines (S. Kakar, A. Askari and K. Garlid, in preparation). The existence of the latter class of antiporter in plasmalemma may seem unlikely at first glance, since it would tend to catalyze Na+/K+ exchange and dissipate the effects of the Na+,K+-ATPase. Nevertheless, a sound design principle would be followed if the cell, like mitochondria, were to regulate volume by governing a passive back-flow process rather than an active transport process. In conclusion, it seems premature to conclude that plasma membranes contain only one type of Na+/H+ antiporter. Nor does it seem likely that there is an unlimited variety of such transporters. I propose as a working hypothesis that antiporters from both mitochondria and plasmalemma may be separated into two classes: Na+-selective and non-Na+-selective.(ABSTRACT TRUNCATED AT 400 WORDS)
Garlid
K D
KD
Department of Pharmacology and Therapeutics, Medical College of Ohio, Toledo 43699.
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D007700:Kinetics; D008027:Light; D008274:Magnesium / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D027961:Potassium-Hydrogen Antiporters; D051381:Rats; D012542:Scattering, Radiation; D017923:Sodium-Hydrogen Exchangers; D013367:Submitochondrial Particles / Q000378:metabolism*
D002352:Carrier Proteins; D027961:Potassium-Hydrogen Antiporters; D017923:Sodium-Hydrogen Exchangers; D008274:Magnesium; D011188:Potassium