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, ≈5 mmol/L), partially stereospecific for L-lactate over D-lactate, and inhibited by 55±7% and 82±7% by the monocarboxylate carrier inhibitors α-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+.