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. 1991 Sep;441:673–684. doi: 10.1113/jphysiol.1991.sp018772

Alpha 1-adrenoceptors reduce background K+ current in rabbit ventricular myocytes.

D Fedida 1, A P Braun 1, W R Giles 1
PMCID: PMC1180219  PMID: 1667803

Abstract

1. Ventricular myocytes were isolated by enzymatic dispersion of adult rabbit hearts, and voltage clamped using the whole-cell variation of the patch clamp technique. Experiments were carried out at either 35 degrees C or room temperature (21-23 degrees C). 2. In the presence of 10(-3) M-4-aminopyridine to block the transient outward K+ current, and 10(-6) M-propranolol to block beta-adrenoceptors, the alpha 1-adrenergic agonist methoxamine produced action potential prolongation, and a small depolarization of the diastolic membrane potential. Under voltage clamp conditions, methoxamine decreased the magnitude of the inward rectifier K+ current, IK1, in both the inward and outward directions. This effect was dose dependent (10(-5)-10(-3) M) and fully reversible upon wash-out of the agonist. 3. The neurotransmitter noradrenaline (10(-6)-2 x 10(-5) M), in the presence of propranolol (10(-6) M), also reduced IK1 in ventricular cells, and this effect was blocked by the specific alpha 1-adrenoceptor antagonist prazosin. 4. The alpha 1-adrenoceptor-mediated decrease in IK1 in ventricular myocytes was not affected by pre-incubation of the cells with 0.5 micrograms/ml pertussis toxin (8-10 h, 30-32 degrees C). This result suggests that in rabbit ventricular cells, the alpha 1-modulation of IK1 occurs via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein. 5. These observations demonstrate that IK1 in ventricular myocytes can be modulated by cardiac alpha 1-adrenoceptors. The resulting changes in action potential repolarization and diastolic membrane potential may have significant effects on cardiac performance.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Apkon M., Nerbonne J. M. Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8756–8760. doi: 10.1073/pnas.85.22.8756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benfey B. G. Cardiac alpha adrenoceptors. Can J Physiol Pharmacol. 1980 Oct;58(10):1145–1157. doi: 10.1139/y80-174. [DOI] [PubMed] [Google Scholar]
  3. Boyett M. R., Fedida D. Changes in the electrical activity of dog cardiac Purkinje fibres at high heart rates. J Physiol. 1984 May;350:361–391. doi: 10.1113/jphysiol.1984.sp015206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boyett M. R., Fedida D. The effect of heart rate on the membrane currents of isolated sheep Purkinje fibres. J Physiol. 1988 May;399:467–491. doi: 10.1113/jphysiol.1988.sp017092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braun A. P., Fedida D., Clark R. B., Giles W. R. Intracellular mechanisms for alpha 1-adrenergic regulation of the transient outward current in rabbit atrial myocytes. J Physiol. 1990 Dec;431:689–712. doi: 10.1113/jphysiol.1990.sp018355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brückner R., Mügge A., Scholz H. Existence and functional role of alpha 1-adrenoceptors in the mammalian heart. J Mol Cell Cardiol. 1985 Jul;17(7):639–645. doi: 10.1016/s0022-2828(85)80063-8. [DOI] [PubMed] [Google Scholar]
  7. Buxton I. L., Brunton L. L. Action of the cardiac alpha 1-adrenergic receptor. Activation of cyclic AMP degradation. J Biol Chem. 1985 Jun 10;260(11):6733–6737. [PubMed] [Google Scholar]
  8. Böhm M., Schmitz W., Scholz H. Evidence against a role of a pertussis toxin-sensitive guanine nucleotide-binding protein in the alpha 1-adrenoceptor-mediated positive inotropic effect in the heart. Naunyn Schmiedebergs Arch Pharmacol. 1987 Apr;335(4):476–479. doi: 10.1007/BF00165566. [DOI] [PubMed] [Google Scholar]
  9. Endoh M., Schümann H. J. Frequency-dependence of the positive inotropic effect of methoxamine and naphazoline mediated by alpha-Adrenoceptors in the isolated rabbit papillary muscle. Naunyn Schmiedebergs Arch Pharmacol. 1975;287(4):377–389. doi: 10.1007/BF00500039. [DOI] [PubMed] [Google Scholar]
  10. Fabiato A., Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 1979;75(5):463–505. [PubMed] [Google Scholar]
  11. Fedida D., Shimoni Y., Giles W. R. A novel effect of norepinephrine on cardiac cells is mediated by alpha 1-adrenoceptors. Am J Physiol. 1989 May;256(5 Pt 2):H1500–H1504. doi: 10.1152/ajpheart.1989.256.5.H1500. [DOI] [PubMed] [Google Scholar]
  12. Fedida D., Shimoni Y., Giles W. R. Alpha-adrenergic modulation of the transient outward current in rabbit atrial myocytes. J Physiol. 1990 Apr;423:257–277. doi: 10.1113/jphysiol.1990.sp018021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Flavahan N. A., McGrath J. C. alpha 1-adrenoceptors can mediate chronotropic responses in the rat heart. Br J Pharmacol. 1981 Jul;73(3):586–588. doi: 10.1111/j.1476-5381.1981.tb16791.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Giles W. R., Imaizumi Y. Comparison of potassium currents in rabbit atrial and ventricular cells. J Physiol. 1988 Nov;405:123–145. doi: 10.1113/jphysiol.1988.sp017325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Giotti A., Ledda F., Mannaioni P. F. Effects of noradrenaline and isoprenaline, in combination with - and -receptor blocking substances, on the action potential of cardiac Purkinje fibres. J Physiol. 1973 Feb;229(1):99–113. doi: 10.1113/jphysiol.1973.sp010129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hauswirth O., Wehner H. D., Ziskoven R. alpha-Adrenergic receptors and pacemaker current in cardiac Purkinje fibres. Nature. 1976 Sep 9;263(5573):155–156. doi: 10.1038/263155a0. [DOI] [PubMed] [Google Scholar]
  17. Hescheler J., Nawrath H., Tang M., Trautwein W. Adrenoceptor-mediated changes of excitation and contraction in ventricular heart muscle from guinea-pigs and rabbits. J Physiol. 1988 Mar;397:657–670. doi: 10.1113/jphysiol.1988.sp017024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hume J. R., Uehara A. Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes. J Physiol. 1985 Nov;368:525–544. doi: 10.1113/jphysiol.1985.sp015874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Luetje C. W., Tietje K. M., Christian J. L., Nathanson N. M. Differential tissue expression and developmental regulation of guanine nucleotide binding regulatory proteins and their messenger RNAs in rat heart. J Biol Chem. 1988 Sep 15;263(26):13357–13365. [PubMed] [Google Scholar]
  20. Nakashima M., Tsuru H., Shigei T. Stimulant action of methoxamine in the isolated atria of normal and 6-propyl-2-thiouracil-fed rats. Jpn J Pharmacol. 1973 Jun;23(3):307–312. doi: 10.1254/jjp.23.307. [DOI] [PubMed] [Google Scholar]
  21. Pappano A. J. Propranolol-insensitive effects of epinephrine on action potential repolarization in electrically driven atria of the guinea pig. J Pharmacol Exp Ther. 1971 Apr;177(1):85–95. [PubMed] [Google Scholar]
  22. Posner P., Farrar E. L., Lambert C. R. Inhibitory effects of catecholamines in canine cardiac Purkinje fibers. Am J Physiol. 1976 Nov;231(5 Pt 1):1415–1420. doi: 10.1152/ajplegacy.1976.231.5.1415. [DOI] [PubMed] [Google Scholar]
  23. Ravens U., Wang X. L., Wettwer E. Alpha adrenoceptor stimulation reduces outward currents in rat ventricular myocytes. J Pharmacol Exp Ther. 1989 Jul;250(1):364–370. [PubMed] [Google Scholar]
  24. Rosen M. R., Hordof A. J., Ilvento J. P., Danilo P., Jr Effects of adrenergic amines on electrophysiological properties and automaticity of neonatal and adult canine Purkinje fibers: evidence for alpha- and beta-adrenergic actions. Circ Res. 1977 Apr;40(4):390–400. doi: 10.1161/01.res.40.4.390. [DOI] [PubMed] [Google Scholar]
  25. Rosen M. R., Steinberg S. F., Chow Y. K., Bilezikian J. P., Danilo P., Jr Role of a pertussis toxin-sensitive protein in the modulation of canine Purkinje fiber automaticity. Circ Res. 1988 Feb;62(2):315–323. doi: 10.1161/01.res.62.2.315. [DOI] [PubMed] [Google Scholar]
  26. Satoh H., Hashimoto K. Effect of alpha 1-adrenoceptor stimulation with methoxamine and phenylephrine on spontaneously beating rabbit sino-atrial node cells. Naunyn Schmiedebergs Arch Pharmacol. 1988 Apr;337(4):415–422. doi: 10.1007/BF00169533. [DOI] [PubMed] [Google Scholar]
  27. Schmitz W., Scholz H., Scholz J., Steinfath M., Lohse M., Puurunen J., Schwabe U. Pertussis toxin does not inhibit the alpha 1-adrenoceptor-mediated effect on inositol phosphate production in the heart. Eur J Pharmacol. 1987 Feb 24;134(3):377–378. doi: 10.1016/0014-2999(87)90374-8. [DOI] [PubMed] [Google Scholar]
  28. Sen L., Liang B. T., Colucci W. S., Smith T. W. Enhanced alpha 1-adrenergic responsiveness in cardiomyopathic hamster cardiac myocytes. Relation to the expression of pertussis toxin-sensitive G protein and alpha 1-adrenergic receptors. Circ Res. 1990 Nov;67(5):1182–1192. doi: 10.1161/01.res.67.5.1182. [DOI] [PubMed] [Google Scholar]
  29. Shah A., Cohen I. S., Rosen M. R. Stimulation of cardiac alpha receptors increases Na/K pump current and decreases gK via a pertussis toxin-sensitive pathway. Biophys J. 1988 Aug;54(2):219–225. doi: 10.1016/S0006-3495(88)82950-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steinberg S. F., Kaplan L. M., Inouye T., Zhang J. F., Robinson R. B. Alpha-1 adrenergic stimulation of 1,4,5-inositol trisphosphate formation in ventricular myocytes. J Pharmacol Exp Ther. 1989 Sep;250(3):1141–1148. [PubMed] [Google Scholar]
  31. Tung L. H., Rand M. J., Louis W. J. Cardiac alpha-adrenoceptors involving positive chronotropic responses. J Cardiovasc Pharmacol. 1985;7 (Suppl 6):S121–S126. doi: 10.1097/00005344-198500076-00020. [DOI] [PubMed] [Google Scholar]

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