Abstract
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 (≥ 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.
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Bkaily G, Sperelakis N: Injection of guanosine 5′-cyclic monophosphate into heart cells blocks calcium slow channels. Am J Physiol 248:H745-H749, 1985
Wahler GM, Sperelakis N: Effects of cyclic GMP on single K channel currents in cultured embryonic chick hearts. Fed Proc 45:511, 1986a (Abst)
Wahler GM, Sperelakis N: Cyclic GMP initially causes inhibition of cardiac single K channel currents followed by appearance of long openings. Circulation 74, Suppl II:255, 1986b (Abst)
McLean MJ, Sperelakis N: Retention of fully differentiated electrophysiological properties of chick embryonic heart cells in culture. Devel Biol 50:134–141, 1976
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth F: Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100, 1981
Miller JP, Boswell KH, Muneyama K, Simon LN, Robins RK, Shuman DA: Synthesis and biochemical studies of various 8-substituted derivatives of guanosine- 3′,5′-cyclic phosphate, and xanthosine 3′,5′-cyclic phosphate. Biochem 12:5310–5319, 1973
Lincoln TM, Corbin JD: Characterization and biological role of the cGMP-dependent protein kinase. Adv Cyclic Nucl Res 15:139–192, 1983
Sakmann B, Trube G: Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol 347:641–657, 1984a
Sakmann B, Trube G: Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol 347:659–683, 1984b
Kurachi Y: Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guinea-pig heart. J Physiol 366:365–385, 1985
Trube G, Hescheler J: Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches. Pflugers Arch 401:178–184, 1984
Payet MD, Rousseau E, Sauve R: Single-channel analysis of a potassium inward rectifier in myocytes of newborn rat heart. J Memb Biol 86:79–88, 1985
Soejima MA, Noma A: Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflugers Arch 400:424–431, 1984
Kurachi Y, Nakajimo T, Sugimoto T: Acetylcholine activation of K+ channels in cell-free membrane of atrial cells. Am J Physiol 251:H681-H684, 1986
Pfaffinger PJ, Martin JM, Hunter DD, Nathanson NM, Hille B: GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Nature 317:536–538, 1985
Sorota S, Tsuji Y, Tajima T, Pappano A: Pertussis toxin treatment blocks hyperpolarization by muscarinic agonists in chick atrium. Cric Res 57:748–758, 1985
Yatani A, Codina J, Brown AM, Birnbaumer L: Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk. Science 235:207–211, 1987
Hino N, Ochi R: Effect of acetylcholine on membrane currents in guinea-pig papillary muscle. J Physiol 307:183–197, 1980
Bubien JK, Woods WT: Selective effects of acetylcholine and succinylcholine on potassium channels in heart cells. Physiologist 29:163, 1986 (Abst)
Carmeliet E, Ramon J: Effect of acetylcholine on time-independent currents in sheep cardiac Purkinje fibers. Pflugers Arch 387:207–216, 1980
Carmeliet E, Mubagwa K: Changes by acetylcholine of membrane currents in rabbit cardiac Purkinje fibers. J PHysiol 371:201–217, 1986
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Wahler, G.M., Sperelakis, N. Use of the cell-attached patch clamp technique to examine regulation of single cardiac K channels by cyclic GMP. Mol Cell Biochem 80, 27–35 (1989). https://doi.org/10.1007/BF00231001
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DOI: https://doi.org/10.1007/BF00231001