Skip to main content
SpringerLink
Log in

Modulation of the inwardly rectifying K+ channel in isolated human atrial myocytes by α1-adrenergic stimulation

  • Articles
  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

We have examined the α1-adrenergic modulation of the inwardly-rectifying K+ channel (I K1) in isolated human atrial myocytes using the patch clamp technique. α1-Adrenergic agonist methoxamine produced action potential prolongation and a depolarization of the resting membrane potential. Under whole-cell voltage clamp conditions, bath application of methoxamine can inhibit macroscopic I K1. The methoxamine-induced inhibition was reversible and concentration dependent, with the concentration for half-maximal inhibition being 18 μm. The methoxamine-induced inhibition of I K1 was prevented by bath application of α1-adrenergic blocker prazosin. The current was similarly inhibited by phorbol ester (PMA), an activator of protein kinase C (PKC). In contrast, methoxamine failed to inhibit the current in the presence of a specific PKC inhibitor H-9, suggesting that PKC is involved in the methoxamine-induced inhibition of I K1. In single channel recording from cell attached patches, bath-applied methoxamine could suppress I K1 channels by decreasing the frequency and duration of bursting without affecting unitary amplitude. Direct application of purified PKC to excised inside-out patches inhibited channel activity similar to methoxamine in cell-attached patches. The PKC selective inhibitor, PKC19-36, prevented the PKC-induced inhibition of the channel. We conclude that human atrial I K1 can be inhibited by α1-adrenergic stimulation via PKC-dependent pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ashford, M.L.J., Bond, C.T., Blair, T.A., Adelman, J.P. 1994. Cloning and functional expression of a rat heart K ATP channel. Nature 370:456–459

    Google Scholar 

  • Alexander, D.R., Hexham, J.M., Lucas, S.C., Graves, J.D., Cantrell, D.A., Crumpton, M.J. 1989. A protein kinase C pseudosubstrate peptide inhibits phosphorylation of the CD3 antigen in streptolysin-O-permeabilized human T lymphocytes. Biochem. J. 260:893–901

    Google Scholar 

  • Apkon, M., Nerbonne, J.M. 1988. α1-Adrenergic agonists selectively suppress voltage-dependent K+ currents in rat ventricular myocytes. Proc. Natl. Acad. Sci. USA 85:8756–8760

    Google Scholar 

  • Berridge, M.J., Irvine, R.F. 1984. Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321

    Google Scholar 

  • Braun, A.P., Fedida, D., Giles, W.R. 1992. Activation of α1-adrenoceptors modulates the inwardly rectifying potassium currents of mammalian atrial myocytes. Pfluegers Arch. 421:431–439

    Google Scholar 

  • Colquhoun, D., Sigworth, F.J. 1983. Fitting and statistical analysis of single-channel records. In: Single-Channel Recording. B. Sakmann and E. Neher, editors, pp. 191–263. Plenum Press, New York

    Google Scholar 

  • Coraboeuf, E., Nargeot, J. 1993. Electrophysiology of human cardiac cells. Cardiovas. Res. 27:713–1725

    Google Scholar 

  • Corr, P.B., Yamada, K.A., Witkowski, F.X. 1986. Mechanisms controlling cardiac autonomic function and their relationship to arrhythmogenesis. In: The Heart and Cardiovascular System. H.A. Fozzard, E. Haber, R. Jennings, A. Katz, and H. Mogan, editors, pp. 1343–404. Raven Press, New York

    Google Scholar 

  • Dascal, N., Schreibmayer, W., Lim, N.F., Wang, W., Chavkin, C., DiMango, L., Labarca, C., Kieffer, B.L., Gaveriaux-Ruff, C., Trollinger, D., Lester, H.A., Davidson, N. 1993. Atrial G proteinactivated K+ channel:expression cloning and molecular properties. Proc. Natl. Acad. Sci. USA 90:10235–10239

    Google Scholar 

  • Exton, J.H. 1985. Role of calcium and phosphoinositides in the actions of certain hormones and neurotransmitters. J. Clin. Invest. 254:9829–9834

    Google Scholar 

  • Fedida, D., Braun, A.P., Giles, W.R. 1991. α1-Adrenoceptors reduce background K+ current in rabbit ventricular myocytes. J. Physiol. 441:673–684

    Google Scholar 

  • Fedida, D., Braun, A.P., Giles, W.R. 1993. α1-Adrenoceptors in myocardium: functional aspects and transmembrane signaling mechanisms. Physiol. Rev. 73:469–487

    Google Scholar 

  • Fedida, D., Shimoni, Y., Giles, W.R. 1989. A novel effect of norepinephrine on cardiac cells is mediated by α1-adrenoceptors. Am. J. Physiol. 256:H1500-H1504

    Google Scholar 

  • Fedida, D., Shimoni, Y., Giles, W.R. 1990. α1-Adrenergic modulation of the transient outward current in rabbit atrial myocytes. J. Physiol. 423:257–277

    Google Scholar 

  • Ferry, D.R., Kaumann, A.J. 1987. Relationship between betaadrenoceptors and calcium channels in human ventricular myocardium. Br. J. Pharmacol. 9046:447–457

    Google Scholar 

  • Hamill, O.P., Marty, A., Neher, E., Sakmann, B., Sigworth, F.J. 1981. Improved patch clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pfluegers Arch. 391:85–100

    Google Scholar 

  • Heidbuchel, H., Vereecke, J., Carmeliet, E. 1990. Three different potassium channels in human atrium: Contribution to the basic potassium conductance. Circ. Res. 66:1277–1286

    Google Scholar 

  • House, C., Kemp, B. 1987. Protein kinase C contains a pseudosubstrate prototope in its regulatory domain. Science 238:11726–728

    Google Scholar 

  • Isenberg, G., Klockner, U. 1982. Calcium tolerant ventricular myocytes prepared by preincubation in KB medium. Pfluegers Arch. 395:6–18

    Google Scholar 

  • Jahnel, U., Jakob, H., Nawrath, H. 1992. Electrophysiologic and inotropic effects of α-adrenoceptor stimulation in human isolated atrial heart muscle. N-S. Arch. Pharmacol. 346:82–87

    Google Scholar 

  • Jahnel, U., Nawrath, H., Carmeliet, E., Vereecke, J. 1991. Depolarization-induced influx of sodium in response to phenylephrine in rat atrial heart muscle. J. Physiol. 432:621–637

    Google Scholar 

  • Koumi, S-i., Sato, R., Aramaki, T. 1994a. Characterization of the calcium-activated chloride channel in isolated guinea-pig hepatocytes. J. Gen. Physiol. 104:357–373

    Google Scholar 

  • Koumi, S-i., Arentzen, C.E., Backer, C.L., Wasserstrom, J.A. 1994b. Alterations in muscarinic K+ channel response to acetylcholine and G protein-mediated activation in atrial myocytes isolated from failing human hearts. Circulation 90:2213–2224

    Google Scholar 

  • Koumi, S-i., Backer, C.L., Arentzen, C.E. 1995. Characterization of the inwardly-rectifying K+ channel in human cardiac myocytes: Alterations in channel behavior in myocytes isolated from patients with idiopathic dilated cardiomyopathy. Circulation 92:164–174

    Google Scholar 

  • Koumi, S-i., Sato, R., Horikawa, T., Aramaki, T., Okumura, H. 1994c. Characterization of the calcium-sensitive voltage-gated delayed rectifier potassium channel in isolated guinea pig hepatocytes. J. Gen. Physiol. 104:147–171

    Google Scholar 

  • Koumi, S-i., Wasserstrom, J.A. 1994. Acetylcholine-sensitive muscarinic K+ channels in mammalian ventricular myocytes. Am. J. Physiol. 266:H1812-H1821

    Google Scholar 

  • Kubo, Y., Baldwin, T.J., Jan, Y.N., Jan, L.Y. 1993. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature 362:127–133

    Google Scholar 

  • Kubo, Y., Reuveny, E., Siesinger, P.A., Jan, Y.N., Jan, L.Y. 1993. Primary structure and functional expression of a rat G-proteincoupled muscarinic potassium channel. Nature 364:802–806

    Google Scholar 

  • Mazzanti, M., DiFrancesco, D. 1989. Intracellular Ca modulates K-inward rectification in cardiac myocytes. Pfluegers Arch. 413:322–324

    Google Scholar 

  • Mukherjee, A., Haghani, Z., Brady, J., Bush, J., McBride, W., Buja, L.M., Willerson, J.T. 1983. Differences in myocardial α- and β-adrenergic receptor numbers in different species. Am. J. Physiol. 245:H957-H961

    Google Scholar 

  • Nishizuka, Y. 1984. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308:693–698

    Google Scholar 

  • Noble, D. 1984. The surprising heart: a review of recent progress in cardiac electrophysiology. J. Physiol. 351:1–50

    Google Scholar 

  • Nosek, T.M., Williams, M.F., Zeigler, S.T., Godt, R.E. 1986. Inositol triphosphate enhances calcium release in skinned cardiac and skeletal muscle. Am. J. Physiol. 250:C807-C811

    Google Scholar 

  • Ravens, U., Wang, X-L., Wettwer, E. 1989. Alpha adrenoceptor stimulation reduces outward currents in rat ventricular myocytes. J. Pharmacol. Exp. Ther. 250:364–370

    Google Scholar 

  • Saffitz, J.E. 1989. Distribution of α1-adrenergic receptors in myocytic regions and vasculature of feline myocardium. Am. J. Physiol. 257:H162-H169

    Google Scholar 

  • Sato, R., Hisatome, L, Wasserstrom, J.A., Arentzen, C.E., Singer, D.H. 1990. Acetylcholine-sensitive potassium channels in human atrial myocytes. Am. J. Physiol. 259:H1730-H1735

    Google Scholar 

  • Shah, A., Cohen, I.S., Rosen, M.R. 1988. Stimulation of cardiac alpha receptors increases Na/K pump current and decreases gK via a pertussis toxin-sensitive pathway. Biophys. J. 54:219–225

    Google Scholar 

  • Snyders, D.J., Po, S.S., Tamkun, M.M., Bennett, P.B. 1992. High affinity state-dependent block of a cloned human cardiac K+ channel by 4-aminopyridine. Circulation 86:Suppl. I:I-26 (Abstr.)

    Google Scholar 

  • Sterb, H., Irvine, R.F., Berridge, M.J., Schultz, I. 1983. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-l,4,5-triphosphate. Nature 306:67–69

    Google Scholar 

  • Suzuki, M., Morita, T., Hanaoka, K., Kawaguchi, Y., Sakai, O. 1991. A Cl− channel activated by parathyroid hormone in rabbit renal proximal tubule cells. J. Clin. Invest. 88:735–742

    Google Scholar 

  • Tamkun, M.M., Knoth, K.M., Walbridge, J.A., Kroemer, H., Roden, D.M., Glover, D.M. 1991. Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricule. FASEB. J. 5:331–337

    Google Scholar 

  • Wible, B.A., De Biasi, M., Majumder, K., Taglialatela, M., Brown, A.M. 1995 Cloning and functional expression of an inwardly rectifying K+ channel from human atrium. Circ Res. 76:343–350

    Google Scholar 

  • Woodgett, J.R., Hunter, T. 1987. Isolation and characterization of two distinct forms of protein kinase. C. J. Biol. Chem. 262:4836–4843

    Google Scholar 

  • Yue, D.T., Marban, E. 1988. A novel cardiac potassium channel that is active and conductive at depolarized potentials. Pfluegers Arch. 413:127–133

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 60611, Chicago, IL

    R. Sato

  2. Department of Medicine, Northwestern University Medical School, 60611, Chicago, IL

    S-i. Koumi

  3. First Department of Medicine, Kinki University School of Medicine, 589, Osaka

    R. Sato

  4. First Department of Medicine, Nippon Medical School, 113, Tokyo, Japan

    S-i. Koumi

Authors
  1. R. Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S-i. Koumi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sato, R., Koumi, Si. Modulation of the inwardly rectifying K+ channel in isolated human atrial myocytes by α1-adrenergic stimulation. J. Membarin Biol. 148, 185–191 (1995). https://doi.org/10.1007/BF00207274

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00207274

Key words

Search

Navigation