Distribution of lactate and other ions in inactive skeletal muscle: influence of hyperkalemic lactacidosis.
The purpose of this study was to quantify changes in intracellular ion and acid-base status resulting from the net flux of ions between perfusate and noncontracting muscle of differing fibre type in response to a perfusate that simulated the ionic conditions seen during intense exercise. Isolated rat hind limbs were perfused for 80 min with a bovine erythrocyte perfusate. Two series of experiments were performed: a normal perfusate (NP, n = 8) or a lactacidotic perfusate (LP, n = 8) that simulated arterial plasma and blood composition during intense exercise ([Lac-] = 11.0 mequiv. L-1, [K+] = 7.5 mequiv. L-1, and nonvolatile acid concentration = 71 nequiv.L-1). Net ion fluxes were determined by the arteriovenous difference across the hind limb and perfusate flow. Muscle ion concentrations were measured in the soleus (SOL), plantaris (PLT), and white gastrocnemius (WG) muscles. In the NP group, small net effluxes of K+ and Lac- from muscle were observed, but there was no net flux of Na+ or CI-. During LP, an initial rapid net influx of Lac- into muscle (151.2 +/- 9.4 mu equiv. min-1. 100 g-1 at 5 min) was followed by a steady-state net influx of 24-37 mu equiv. min-1. 100 g-1 between 20 and 60 min. During LP, net influx of Na+, CI-, and K+ was greater than during NP and average 58.0 +/- 11.2, 30.0 +/- 7.5, and 7.5 +/- 1.9 mu equiv. min-1. 100 g-1, respectively. Following LP, muscle content of Na+ (WG only) and Lac- (WG, PLT, and SOL) was increased to a greater extent than following NP. The increased [Lac-]i contributed to an elevated [H+]i only in the slow oxidative SOL, consistent with the higher concentration of Lac- transporters, lower capacity to bind protons, and better regulation of [Na+]i in slow oxidative muscles. Calculated membrane potential (Em) was unchanged with NP but decreased on average from -76.2 +/- 1.2 to 63.4 +/- 2.2 mV with LP perfusion, with no difference among fibre types. The steady-state distribution of Lac- across the sarcolemma appears to be a function of both metabolic and transport processes; specifically, Lac- distribution was not fully explained by the membrane potential nor by the nonionic distribution of HLac as determined by the transmembrane pH gradient. It is concluded that inactive skeletal muscle modifies the ionic composition of blood perfusing the muscles. However, the altered ionic composition of these muscles may compromise their function as a result of an altered membrane potential in fast and slow muscles and increased [H+]i in slow oxidative muscles.
Chin
E R
ER
Department of Medicine, McMaster University Medical Center, Hamilton, ON, Canada.
Lindinger
M I
MI
Heigenhauser
G J
GJ
D000140:Acidosis, Lactic / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D006947:Hyperkalemia / Q000378:metabolism* / Q000503:physiopathology; D017136:Ion Transport; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D011189:Potassium Chloride / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism
D019344:Lactic Acid; D012965:Sodium Chloride; D011189:Potassium Chloride