Quinine inhibition of Na+ and K+ transport provides evidence for two cation/H+ exchangers in rat liver mitochondria.

Kinetic properties of the sodium/hydrogen ion antiport of heart mitochondria

“…It should be noted that studies of the pH dependency of the rate of osmotic swelling of mitochondria in sodium acetate (Brierley et al 1978; Nakashima & Garlid, 1982) or in NaCl following the induction of CL/OH" antiport with tripropyltin (Brierley et al 1978) have shown an optimum pH0 near 7.3 and that both of these reactions are thought to be limited by Na+/H+ antiport. BCECF fluorescence shows that pH¡ is very nearly equal to pH0 under both of these conditions (data not shown).…”

“…The respiration-dependent uptake of Na+ by SMP has also been attributed to this antiport (Douglas & Cockrell, 1973), as has respiration-dependent extrusion of accumulated Na+ from intact mitochondria (Brierley et al, 1977). These studies indicate that the Na+/H+ antiport is specific for Na+ and Li+ (Brierley et al, 1978;Rosen & Futai, 1980), has a pH0 optimum near 7.3 in acetate (Brierley et al, 1978), and is insensitive to quinine, divalent cations, and DCCD (Nakashima & Garlid, 1982;Garlid, 1988a). These properties permit the Na+/H+ antiport to be distinquished from the K+/H+ exchanger, an antiporter that becomes apparent in swollen or Mg2+-depleted mitochondria (Brierley & Jung, 1988a,b;Garlid, 1988a) and which appears capable of transporting Na+ and Li+, as well as K+.…”

“…overt Na+/H+ antiport and a latent K+/H+ exchange component [see Brierley (1983), Jung (1988a,b), andGarlid (1988a,b) for recent reviews]. The activity of the Na+/H+ antiport has been followed by the passive osmotic swelling of mitochondria in acetate salts (Mitchell & Moyle, 1969b;Brierley et al, 1978;Nakashima & Garlid, 1982), by glass electrode records of Na+-dependent changes in the pH of the suspending medium of either mitochondria (Mitchell & Moyle, 1967; Crompton & Heid, 1978) or SMP (Papa et al, 1973), and by changes in quinacrine fluorescence in energized SMP (Rosen & Futai, 1980;Brierley et al, 1984).…”

LETM1: Essential for Mitochondrial Biology and Cation Homeostasis?

“…Submitochondrial particle (SMP): a MIM fragment obtained from osmotically shocked mitochondria (mitoplasts) that has formed an inside-out vesicle as a result of the loss of mitochondrial invaginations when exposed to ultrasound. antiporter (NHE) that is specific for Na + , matrix K + can be released only by the KHE, a promiscuous monovalent cation antiporter [44]. With its function of removing excess matrix K + imported by K + channels, the KHE is a key component of the K + cycle that crucially regulates matrix volume [3].…”

The principal mitochondrial K+ uniport is associated with respiratory complex I

“…In order to understand the relative contribution of K + and Na + ions to the currents reported here, we chose two compounds that were employed in the past to discriminate between K + versus Na + uniporter(s) and exchanger(s) of the mitochondrial membrane: quinine and 5-N-ethyl-N-isopropyl amiloride (EIPA) (Brierley, Baysal et al 1994, Bernardi 1999). Previous reports had argued that quinine inhibited the non-selective mitochondrial K + uniporter as well as the non-selective K + /Na + /Li + -H + exchanger (KHE) (Nakashima and Garlid 1982, Jung, Farooqui et al 1984, Bernardi 1999, whereas EIPA specifically inhibited the selective Na + -H + exchanger (NHE) (Brierley, Baysal et al 1994, Bernardi 1999). Surprisingly, both EIPA and quinine equally affected K + and Na + currents at the doses used to discriminate and inhibit the aforementioned uniporter and exchangers of the IMM (Fig.…”