ELEVATION OF INTRACELLULAR CALCIUM BY MUSCARINIC RECEPTOR ACTIVATION INDUCES A BLOCK OF VOLTAGE-ACTIVATED RAT ETHER-A-GO-GO CHANNELS IN A STABLY TRANSFECTED CELL-LINE

We have studied the properties of r-eag voltage-activated potassium ch annels in a stably transfected human embryonic kidney cell line, it wa s found that r-eag channels are rapidly and reversibly inhibited by a rise in intracellular calcium from 30 to 300 nM. The inhibition does n ot appear to depend on the activity of calcium-dependent kinases and p hosphatases. The effect of calcium on r-eag channel activity was studi ed in inside-out membrane patches. Calcium inhibited r-eag channel act ivity with a mean IC50 of 67 nM. Activation of muscarinic receptors, g enerating calcium oscillations in the transfected cells, induced a syn chronous inhibition of r-eag mediated outward currents. This shows tha t calcium can mediate r-eag current inhibition following muscarinic re ceptor activation. The data indicate that r-eag channels are calcium-i nhibitable voltage-activated potassium channels.