LACTATE TRANSPORT IN MAMMALIAN VENTRICLE - GENERAL-PROPERTIES AND RELATION TO K+ FLUXES

Net cellular L-lactate efflux associated with accelerated anaerobic gl ycolysis has been implicated as a potential cause of the marked cellul ar K+ loss contributing to lethal cardiac arrhythmias in ischemic hear t and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lactate movement in the heart, isola ted 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 pH(o) (7.35) caused an int racellular acidification averaging 0.181+/-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 electrogen ic current was associated with H+-coupled L-lactate influx, and membra ne potential (-75 to +75 mV) had no effect on the degree of acidificat ion produced by 30 mmol/L [L(-)](o), indicating that L-lactate influx was predominantly nonelectrogenic. Acidification in response to increa sed [L(-)](o) was saturable (K-m, approximate to 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-hy droxycinnamate and mersalyl acid, respectively, consistent with a carr ier-mediated transport mechanism. Extracellular K+ inhibited H+-couple d L-lactate influx by 36+/-2%, suggesting that Kf 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 dur ing exposure to 30 mmol/L [L(-)](o), suggesting that only a minor comp onent, if any, of L-lactate influx was cotransported or codiffused wit h K+.