ABSTRACT
A variety of potassium (K) channels exist in the heart and coronary circulation which subserve a number of different functions. These channels have been shown to be regulated by several factors which include the membrane potential, intracellular Na + and Ca2+ concentrations, arachidonic acid and other fatty acid derivatives. Some of these K channels have also been shown to be modulated by membrane receptors and G proteins (Lazdunski, 1992). More recently, a time independent K channel has been identified which is activated during ischemia and results in K + loss from the myocardium and shortening of the cardiac action potential. This outward current was shown by Noma (1983) to be regulated by the intracellular concentration of A TP in guinea pig ventricular myocytes and this channel was named the A TPregulated or dependent K channel (KATP). Since this original study (Noma, 1983), KATP channel activity has been shown to be modulated by a number of factors such as the ATP / ADP ratio, various nucleotide diphosphates, pH, lactate and oxygenderived free radicals (Nichols and Lederer, 1991). Noma postulated that these channels might serve an endogenous cardioprotective role during the onset of ischemia when followed by timely reperfusion via their ability to accelerate the loss of electrical and contractile activity in the ischemic zone thereby preserving cellular energy reserves and preventing the loss of adenine nucleotides. On the other hand, the loss of cellular K + and shortening of the action potential duration as a result of opening these KATP channels may also result in an increase in electrical inhomogeneity in the myocardium and may result in reentrant-type arrhythmias. Therefore, K channel activators (KCAs) and potassium channel blockers (KCBs) may both be expected to exert beneficial or detrimental effects on the ischemic myocardium and these effects may be determined by a number of factors including drug dose, animal species and, most importantly, by the experimental model and conditions used to study the particular drug of interest.
