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.
Arena
J P
JP
Department of Physiology, University of Rochester School of Medicine and Dentistry, NY.
Walsh
K B
KB
Kass
R S
RS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002417:Cattle; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011690:Purkinje Fibers / Q000187:drug effects / Q000201:enzymology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013696:Temperature
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D007545:Isoproterenol