Membrane ion channels and cardiovascular ATP-sensitive K+ channels

Ion channels are the primary target for a variety of clinically important drugs including local anesthetic, antihypertensive, antianginal, antiarrhythmic, antidiabetic, anticonvulsant hypnotic and anxiolytic agents. Ion channels are specialized proteins inserted in the ion-impermeable cellular membrane, which have a water-filled pore permitting the selective passage of a few biologically important ions (Na+, K+, Ca++ and Cl-) across the membrane. Multiple channels for a given ion can co-exist on the same cell where they have specific functions. The flow of ions through channels produces electrical currents which often act as biological messengers to change and modulate the functional state of the cell. Thus, the influx of Na+ and Ca++ are activating signals whereas the exit of K+ drives the activated cell to a resting state or strengthen the resting state. Interestingly, K+ channels are the most diverse group of ion channels. At least 9 families of K+ channels co-exist in cardiac myocytes where they regulate the heart repolarization and excitability processes under physiological and pathological conditions. ATP-sensitive K+ channels of cardiac myocytes are of particular interest since they have a very high membrane density and are closed under normoxic conditions, becoming operational during ischemic stress when the intracellular levels of ATP decline. Their major function has been proposed to be the preservation of viability of the myocyte during ischemia. ATP-sensitive K+ channels are also present in other tissues, such as the blood vessels, where their opening causes strong relaxing effects. Cardiac and vascular ATP-sensitive K+ channels are the primary target of a novel class of drugs, called K+ channel openers, such as nicorandil and aprikalim.(ABSTRACT TRUNCATED AT 250 WORDS)