Lactate depresses sarcolemmal permeability of Ca 2+ in intact arterial smooth muscle

Abstract

Elevation of ambient lactate concentration has been shown to alter contractile reactivity of vascular smooth muscle. We tested the hypothesis that lactate affects the disposition of intracellular free Ca 2+. Porcine carotid artery strips were incubated in normal medium and in medium containing 10 mM sodium lactate or 10 mM sodium pyruvate. The rate and magnitude of contraction in response to K +-depolarization was depressed in lactate when compared to control. This was associated with a decrease in the onset and magnitude of the normal increase in free [Ca 2+] i, as reflected by fluorescence of fura-2. Pyruvate had no effect on these variables. Depression in [Ca 2+] i could not be attributed to a selective effect of lactate on pH i, membrane potential, or to enhanced superoxide production. Deletion of Ca 2+ from the incubation medium negated depression of contractile responsiveness produced by lactate when compared to control. Lactate had no effect on contraction induced by 100 μM norepinephrine, which releases intracellular stored Ca 2+. Thus, lactate inhibits arterial smooth muscle contraction by inhibiting influx of Ca 2+ across the sarcolemma.