Discrimination by valinomycin K-selective surface microelectrodes of a sulphonylurea-sensitive and a distinct sulphonylurea-, barium-, TEA- and cinnamate-insensitive component of K-efflux from isolated pig coronary arteries during simulated ischaemia

Journal of Clinical and Basic Cardiology 1998; 1 (1): 43-51

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Keywords: Glatte Muskulatur,  Glibenclamid,  Ischämie,  Kalziumkanal,  Sulfonylharnstoff,  glibenclamide,  ischaemia,  K-channel,  smooth muscle,  sulphonylurea

Ischaemia was simulated in isolated pig coronary artery strips by immersing the preparation in paraffin oil. Ion-selective microelectrodes recorded surface potassium (K+s), -pH (pHs) and -Na+ (Na+s) in the thin film of Tyrode solution trapped in the artificially created reduced extracellular space (ARECS) between the hydrophobic liquid ion-selective sensor and the surface of the preparation. The paraffin oil model reproduced two salient characteristics of myocardial ischaemia: surface acidification and K+s, accumulation ? both features have not so far been described in arterial tissue. Sulphonylurea compounds such as glibenclamide (20 µM, 50 µM, 200 µM) and tolbutamide (0.5 mM, 1 mM) as well as a non-sulphonylurea type blocker of K+ATP-channels, tetramethylpyrazine (1 mM), reduced ischaemia-induced K+-accumulation by 66 %. A fraction of the K+-accumulation (33 %) was not sensitive to sulphonylureas and was not affected by Ba2+ (0.3 mM, 1 mM) or tetraethylammonium (TEA; 1 mM). Ischaemia-induced K+-accumulation was unaffected by the known inhibitor of lactic acid transport, alpha-cyano-4hydroxycinnamic acid (4 mM). The removal of external Cl- (leading to the depletion of internal Cl-; Cl- replaced by glucuronate) had no effect upon ischaemia-induced K+ accumulation. During simulated ischaemia there was a fall in pHs. The degree of this acidification was reduced by both amiloride (1 mM) and alpha-cyano-4hydroxycinnamic acid (4 mM). Our results suggest that in isolated pig coronary preparations under conditions of simulated ischaemia, K+-accumulation is partially mediated by a sulphonylurea-sensitive pathway. We consider it likely that this pathway involves the opening of ATP-dependent K+ channels. The source of the sulphonylurea insensitive fraction of K+-accumulation remains unidentified. Furthermore, we conclude that extracellular acidification in these preparation is mediated by both Na+/H+ exchange and the lactic acid carrier. J Clin Basic Cardiol 1998; 1: 43-51.