Modulation of sodium current by lactate in guinea pig ventricular myocytes

• Published in: Cardiovascular research 1994-10, Vol.28 (10), p.1507-1512
• Main Authors: Tanaka, Hideo, Habuchi, Yoshizumi, Lu, Ling-Ling, Furukawa, Taiji, Morikawa, Junichiro, Yoshimura, Manabu
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Biological and medical sciences; Cardiovascular system; Cells, Cultured; Guinea Pigs; heart; Investigative techniques, diagnostic techniques (general aspects); ischaemia; lactate; Lactates - pharmacology; Lactic Acid; Medical sciences; Myocardium - cytology; Myocardium - enzymology; Myocardium - metabolism; Patch-Clamp Techniques; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; sodium current; Sodium-Potassium-Exchanging ATPase - drug effects; surface charge; voltage clamp
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/28.10.1507

Objective: The aim was to elucidate whether or not lactate modifies the fast sodium current (INa) in cardiac cells. Methods: A tight seal whole cell clamp technique was used to record the action potentials and INa, in single ventricular cells from the guinea pig heart. Results: In voltage clamp experiments, superfusion with 20 mM lactate shifted both the normalised conductance (gNa)-voltage relationship and the channel availability curve toward hyperpolarisation by approximately 4 mV, but did not affect the maximum conductance In the test solution containing only CaCl2, as the main divalent component, 20 mM lactate reduced the ionised calcium concentration from 1.02 to 0.84 mM. When the calcium concentration was kept constant by the addition of CaCl2, into the lactate containing solution the lactate effect was nullified. However, a change in the calcium concentration from 1.0 to 0.84 mM without lactate induced a 4 mV negative shift of the channel availability curve. Current clamp experiments in Tyrode solution showed that 20 mM lactate shifted the threshold for the action potential upstroke by 2.5-3 mV, in accordance with the voltage clamp experiments. Conclusions: Lactate modifies INa of ventricular myocytes by shifting its kinetics toward hyperpolarisation. This shift seems to be caused exclusively by a decrease in the ionised divalent cation concentrations and a resultant change in the negative surface charge of the sarcolemma. Cardiovascular Research 1994;28: 1507-1512