Summary
1. The effect of the K+ channel agonist BRL 34915 on membrane conductance was investigated in isolated guinea-pig cardiac myocytes. 2. BRL 34915 reduced the duration of the transmembrane action potential and slightly increased the membrane resting potential in a concentration-dependent manner. 3. BRL 34915 removed the rectification in the steady-state current-voltage relationship. At membrane potentials more negative than the K+ equilibrium potential, membrane conductance was reduced. In the presence of 10−4 mol/l BRL 34915, the current-voltage relationship was linear, i.e. of an ohmic type. 4. The BRL 34915-mediated change in membrane conductance was susceptible to the K+ channel blockers BaCl2 and tetrahydroaminoacridine. 5. In conclusion, BRL 34915 modifies K+ conductance in the cardiac cell membrane. The precise nature of the K+ conductance change remains to be elucidated.
Similar content being viewed by others
References
Allen SL, Boyle JP, Cortijo J, Foster RW, Morgan GP, Small RC (1986) Electrical and mechanical effects of BRL 34915 in guinea-pig isolated trachealis. Br J Pharmacol 89:395–405
Ashwood VA, Buckingham RE, Cassidy F, Evans JM, Faruk EA, Hamilton TC, Nash DJ, Stemp G, Willcocks K (1986) Synthesis and antihypertensive activity of 4-(cyclic amido)-2H-1-benzopyrans. J Med Chem 29:2194–2201
Bechem M, Glitsch HG, Pott L (1983) Properties of an inward rectifying K channel in the membrane of guinea-pig atrial cardioballs. Pflügers Arch 399:186–193
Buckingham RA, Clapham JC, Hamilton TC, Longman SD, Norton J, Poyser RH (1986) BRL 34915, a novel antihypertensive agent: comparison of effect on blood pressure and other haemodynamic parameters with those of nifedipine in animal models. J Cardiovasc Pharmacol 8:798–804
Cain CR, Metzler V (1985) Electrophysiological effects of the antihypertensive agent BRL 34915 on guinea-pig papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol (abstr) 329:R53
Coldwell MC, Howlett DR (1986) BRL 34915 induced potassium channel activation in rabbit isolated mesenteric artery is not calcium dependent. Br J Pharmacol (abstr) 88:443P
Conder ML, McCullough JR (1987) Purported K channel opener, BRL 34915, blocks inwardly rectifying K current in isolated guinea pig ventricular myocytes. Biophys J (abstr) 51:258a
Eisner DA, Vaughan-Jones RD (1983) Do calcium-activated potassium channels exist in the heart? Cell Calcium 4:371–386
Grosset A, Hicks PE (1986) Evidence for blood vessel selectivity of BRL 34915. Br J Pharmacol (abstr) 89:500P
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100
Hamilton TC, Weir SW, Weston AH (1985) Comparison of the effects of BRL 34915 and verapamil on rat portal vein. Br J Pharmacol (abstr) 86:443P
Hamilton TC, Weir SW, Weston AH (1986) Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol 88:103–111
Hille B (1984) Ionic channels of excitable membranes. Sinauer Associates Inc., Sunderland, MA, USA
Inoue T, Ito Y, Takeda K (1983) The effects of 2-nicotinamidoethyl nitrate on smooth muscle cells of the dog mesenteric artery and trachea. Br J Pharmacol 80:459–470
Isenberg G, Klöckner U (1982) Calcium tolerant ventricular myocytes prepared by incubation in a “KB medium”. Pflügers Arch 395:6–18
Kakei M, Yoshinaga M, Saito K, Tanaka H (1986) The potassium current activated by 2-nicotinamidoethyl nitrate (nicorandil) in single ventricular cells of guinea pigs. Proc Roy Soc Lond B229:331–343
Kameyama M, Kakei M, Sato R, Shibasaki T, Matsuda H, Irisawa H (1984) Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature 309:354–356
Kreye VAW, Gerstheimer F, Weston A (1985) Vasodilating drugs with a direct action on smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol (abstr) 330:R1
Kusano K, Barros F, Katz G, Garcia M, Kaczorowski G, Reuben JP (1987) Modulation of K channel activity in aortic smooth muscle by BRL 34915 and a scorpion toxin. Biophys J (abstr) 51:54a
Matsuda H, Saigusa A, Irisawa H (1987) Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature 325:156–159
McDonald TF, Pelzer D, Trautwein W (1984) Cat ventricular muscle treated with D600: effects on calcium and potassium currents. J Physiol 352:203–216
Noble D (1984) The surprising heart: a review of recent progress in cardiac electrophysiology. J Physiol 353:1–50
Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305:147–148
Noma A, Nakayama T, Kwachi Y, Irisawa H (1984) Resting potassium conductances in pacemaker and non-pacemaker heart cells of the rabbit. Jpn J Physiol 34:245–254
Ochi R (1970) The slow inward current and the action of manganese ions in guinea pig's myocardium. Pflügers Arch 316:81–94
Osterrieder W (1987) 9-Amino-1,2,3,4-tetrahydroaminoacridine (THA) is a potent blocker of cardiac potassium channels. Br J Pharmacol 92:521–525
Osterrieder W, Yang Q-F, Trautwein W (1982a) Effects of barium on the membrane currents in the rabbit S-A node. Pflügers Arch 394:78–84
Osterrieder W, Yang Q-F, Trautwein W (1982b) Conductance of the slow inward channel in the rabbit sino-atrial node. Pflügers Arch 394:85–89
Sakmann B, Trube G (1984) Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol 347:641–657
Trautwein W (1973) Membrane currents in cardiac muscle fibers. Physiol Rev 53:793–835
Trube G, Hescheler J (1984) Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches. Pflügers Arch 401:178–184
Weir SW, Weston AH (1986a) Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea-pig taenia caeci. Br J Pharmacol 88:113–120
Weir SW, Weston AH (1986b) The effects of BRL 34915 and nicorandil on electrical and mechanical activity and on 86RB efflux in rat blood vessels. Br J Pharmacol 88:121–128
Yanagisawa T, Taira N (1980) Effect of 2-nicotinamidethyl nitrate (SG-75) on the membrane potential of left atrial muscle fibres of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 312:69–76
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Osterrieder, W. Modification of K+ conductance of heart cell membrane by BRL 34915. Naunyn-Schmiedeberg's Arch Pharmacol 337, 93–97 (1988). https://doi.org/10.1007/BF00169483
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169483