Use of the cell-attached patch clamp technique to examine regulation of single cardiac K channels by cyclic GMP.
Cyclic nucleotides play a central role in the modulation of ion channels in a variety of tissues, including the heart. In order to determine the possible role of cyclic GMP (cGMP) in the regulation of the background K channel activity of cardiac cells, the effect of 8-Br-cGMP on the inwardly-rectifying K channels of cultured ventricular myocytes from embryonic chick hearts was examined. 8-Br-cGMP (10(-4) to 10(-3) M) inhibited these single channel currents within 3 to 10 min. Spontaneous recovery of the currents occurred with prolonged (greater than or equal to 15 min) exposure to 8-Br-cGMP, but this recovery was accompanied by altered channel behavior. Thus, a new long-lasting open state of the channel appeared, in addition to the open state observed prior to 8-Br-cGMP addition. Superfusion of the cells with the muscarinic agonist carbamylcholine (10(-5) M) also resulted in inhibition of the currents, which suggests that the cGMP-mediated inhibition of these channels may occur under physiological conditions. Thus, it appears that cGMP may be an important modulator of the background K conductance (and excitability) of cardiac cells.
Wahler
G M
GM
Department of Physiology and Biophysics, University of Cincinnati, College of Medicine, OH 45267-0576.
Sperelakis
N
N
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002642:Chick Embryo; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000502:physiology*; D016276:Ventricular Function
D007473:Ion Channels; C016276:8-bromocyclic GMP; D002217:Carbachol; D006152:Cyclic GMP; D011188:Potassium