Measurement, block, and modulation of potassium channel currents in the heart

The results with the K+ channel blocking compounds are encouraging because they show a slight structural change in a parent blocking compound can dramatically alter the type of K+ channel blocked by a drug. Our work continues in an effort to determine a more detailed relationship between structural features of a blocker and the type of K+ channel effected. We hope to be able to reveal the requirements for potent and specific blockers of each of these channel types. Selective blockade of these, and other, K+ channels in heart and smooth muscle cells, a goal suggested by the preliminary results presented here, may provide useful tools for more detailed studies of K+ channels. Our experiments also show that temperature can be used to separate the beta-adrenergic regulation of ICa and IDR suggesting different modulatory mechanisms. The results with forskolin show this separation exists at the level of elevated cAMP. This suggests that the K+ and Ca++ channel proteins may be phosphorylated by the same cAMP-dependent protein kinase but with different temperature-sensitive kinetics. It will be interesting to see if this temperature-sensitivity extends to phosphorylation of the channel during intracellular application of cAMP-dependent protein kinase.