Importance of sodium ions in the protective effects of high-potassium, high-glucose solution on electromechanical activities in the guinea-pig myocardium.
The protective effects of high-K, high-glucose solution (GK solution) on electromechanical activity in the isolated guinea-pig ventricular muscle were studied. The basal test solution (basal GK solution) contained 30 mM KCl, 230 mM glucose and 4 mM NaHCO3, that is nominally Ca-free. Various types of GK solutions were also prepared by modifying the composition of this solution. When the muscle was exposed to the basal GK solution, the resting potential fell to about -40 mV, the muscle lost the excitability, and an irreversible contracture gradually developed. This contracture was prevented by elevating [Na]o above 60 mM. Reduction of [K]o to 20 mM, addition of EGTA (0.4 mM), or lowering the temperature (23 degrees C) also suppressed the above contracture. When the GK solution with high Na (106-115 mM NaCl added to basal GK solution in exchange for glucose) was applied, contractures frequently developed upon reintroduction of Tyrode solution (Ca-paradox-like phenomenon). Thus the Ca-free GK solution with 60 mM Na (56 mM NaCl added to basal GK solution in exchange for glucose) induced no contracture, either during or after the test period. Recovery of the action potential after this application was all but complete. On the other hand, addition of 0.9 to 1.8 mM Ca to this solution produced another type of contracture which was sensitive to verapamil. The cardioplegic effects of the Ca-free GK solution with 60 mM Na persisted under hypoxic conditions, and glucose appeared to play a significant role in preventing the hypoxia-related contracture. In contrast, the high-Na (110 mM Na) GK solution containing 0.2 to 0.5 mM Ca and Tyrode solution, both of which produced no contracture under normoxic conditions, did produce contractures under hypoxic conditions. Therefore, Ca-free GK solution containing an appropriate concentration (around 60 mM) of Na may protect the normoxic and hypoxic myocardium against intracellular Ca overload. The related mechanisms involved were discussed with special reference to membrane functions and intracellular Ca-regulating systems.
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006168:Guinea Pigs; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D004533:Egtazic Acid; D012964:Sodium; D014700:Verapamil; D005947:Glucose; D011188:Potassium; D010100:Oxygen; D002118:Calcium