title: Lactate transport in mammalian ventricle. General properties and relation to K+ fluxes.
abstract: Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lactate movement in the heart, isolated guinea pig ventricular myocytes were loaded with the fluorescent H+ or K+ indicators, carboxy SNARF-1 or PBFI, respectively, under whole-cell patch-clamp conditions. With H+ as the only permeable monovalent cation, a rapid increase in extracellular L-lactate concentration ([L-]o) from 0 to 30 mmol/L at constant pHo (7.35) caused an intracellular acidification averaging 0.18 +/- 0.02 pH units in 60 seconds (n = 7), reflecting L-lactate influx in association with H+ influx (or OH- efflux). Under voltage-clamp conditions, no significant electrogenic current was associated with H(+)-coupled L-lactate influx, and membrane potential (-75 to +75 mV) had no effect on the degree of acidification produced by 30 mmol/L [L-]o, indicating that L-lactate influx was predominantly nonelectrogenic. Acidification in response to increased [L-]o was saturable (Km, approximately 5 mmol/L), partially stereospecific for L-lactate over D-lactate, and inhibited by 55 +/- 7% and 82 +/- 7% by the monocarboxylate carrier inhibitors alpha-cyano-4-hydroxycinnamate and mersalyl acid, respectively, consistent with a carrier-mediated transport mechanism. Extracellular K+ inhibited H(+)-coupled L-lactate influx by 36 +/- 2%, suggesting that K+ either inhibited or substituted for H+ in cotransport with L-lactate. However, in myocytes loaded with PBFI, no significant increase in [K+]i was detected during exposure to 30 mmol/L [L-]o, suggesting that only a minor component, if any, of L-lactate influx was cotransported or codiffused with K+.
authors.affiliation: Department of Medicine (Cardiology), UCLA School of Medicine 90024.
authors.forename: R C
authors.initials: RC
authors.lastname: Shieh
authors.forename: J I
authors.initials: JI
authors.lastname: Goldhaber
authors.forename: J S
authors.initials: JS
authors.lastname: Stuart
authors.forename: J N
authors.initials: JN
authors.lastname: Weiss
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D008564:Membrane Potentials; D027501:Monocarboxylic Acid Transporters; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011522:Protons; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D011522:Protons; D019344:Lactic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium