Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1997 Nov 15;505(Pt 1):77–93. doi: 10.1111/j.1469-7793.1997.077bc.x

ATP-dependent desensitization of the muscarinic K+ channel in rat atrial cells.

Z Shui 1, M R Boyett 1, W J Zang 1
PMCID: PMC1160095  PMID: 9409473

Abstract

1. Fast desensitization of the muscarinic K+ channel has been studied in excised patches from rat atrial cells. 2. In inside-out patches, ACh was present in the pipette and GTP was applied via the bath to activate the channel. In outside-out patches, GTP was present in the pipette and ACh was applied via the bath to activate the channel. In both cases, during a 30 s exposure to GTP or ACh there was a decline in channel activity as a result of fast desensitization if ATP was present. 3. In inside-out patches, fast desensitization was still observed if the muscarinic ACh receptor was bypassed and the channel was activated by GTP gamma S. This suggests that fast desensitization is a result of a modification of the channel (or the connecting G protein) and not the receptor. 4. In both inside-out and outside-out patches, channel activity was depressed and fast desensitization was reduced or absent, if ATP was not present. 5. The non-hydrolysable analogue of ATP, AMP-PNP, did not substitute for ATP in its effects on the channel. 6. The results are consistent with the hypothesis that fast desensitization of the muscarinic K+ channel is the result of a dephosphorylation of the channel.

Full text

PDF
77

Images in this article

Selected References

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

  1. Berman D. M., Wilkie T. M., Gilman A. G. GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. Cell. 1996 Aug 9;86(3):445–452. doi: 10.1016/s0092-8674(00)80117-8. [DOI] [PubMed] [Google Scholar]
  2. Boyett M. R., Kirby M. S., Orchard C. H., Roberts A. The negative inotropic effect of acetylcholine on ferret ventricular myocardium. J Physiol. 1988 Oct;404:613–635. doi: 10.1113/jphysiol.1988.sp017309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boyett M. R., Kodama I., Honjo H., Arai A., Suzuki R., Toyama J. Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node. Cardiovasc Res. 1995 Jun;29(6):867–878. [PubMed] [Google Scholar]
  4. Boyett M. R., Roberts A. The fade of the response to acetylcholine at the rabbit isolated sino-atrial node. J Physiol. 1987 Dec;393:171–194. doi: 10.1113/jphysiol.1987.sp016818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heidbüchel H., Callewaert G., Vereecke J., Carmeliet E. ATP-dependent activation of atrial muscarinic K+ channels in the absence of agonist and G-nucleotides. Pflugers Arch. 1990 Apr;416(1-2):213–215. doi: 10.1007/BF00370246. [DOI] [PubMed] [Google Scholar]
  6. Heidbüchel H., Callewaert G., Vereecke J., Carmeliet E. Acetylcholine-mediated K+ channel activity in guinea-pig atrial cells is supported by nucleoside diphosphate kinase. Pflugers Arch. 1993 Jan;422(4):316–324. doi: 10.1007/BF00374286. [DOI] [PubMed] [Google Scholar]
  7. Hong S. G., Pleumsamran A., Kim D. Regulation of atrial muscarinic K+ channel activity by a cytosolic protein via G protein-independent pathway. Am J Physiol. 1996 Feb;270(2 Pt 2):H526–H537. doi: 10.1152/ajpheart.1996.270.2.H526. [DOI] [PubMed] [Google Scholar]
  8. Honjo H., Kodama I., Zang W. J., Boyett M. R. Desensitization to acetylcholine in single sinoatrial node cells isolated from rabbit hearts. Am J Physiol. 1992 Dec;263(6 Pt 2):H1779–H1789. doi: 10.1152/ajpheart.1992.263.6.H1779. [DOI] [PubMed] [Google Scholar]
  9. Kaibara M., Nakajima T., Irisawa H., Giles W. Regulation of spontaneous opening of muscarinic K+ channels in rabbit atrium. J Physiol. 1991 Feb;433:589–613. doi: 10.1113/jphysiol.1991.sp018445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kakei M., Noma A., Shibasaki T. Properties of adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol. 1985 Jun;363:441–462. doi: 10.1113/jphysiol.1985.sp015721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kim D. Beta-adrenergic regulation of the muscarinic-gated K+ channel via cyclic AMP-dependent protein kinase in atrial cells. Circ Res. 1990 Nov;67(5):1292–1298. doi: 10.1161/01.res.67.5.1292. [DOI] [PubMed] [Google Scholar]
  12. Kim D. Mechanism of rapid desensitization of muscarinic K+ current in adult rat and guinea pig atrial cells. Circ Res. 1993 Jul;73(1):89–97. doi: 10.1161/01.res.73.1.89. [DOI] [PubMed] [Google Scholar]
  13. Kim D. Modulation of acetylcholine-activated K+ channel function in rat atrial cells by phosphorylation. J Physiol. 1991 Jun;437:133–155. doi: 10.1113/jphysiol.1991.sp018588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krapivinsky G., Gordon E. A., Wickman K., Velimirović B., Krapivinsky L., Clapham D. E. The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. Nature. 1995 Mar 9;374(6518):135–141. doi: 10.1038/374135a0. [DOI] [PubMed] [Google Scholar]
  15. Kubo Y., Reuveny E., Slesinger P. A., Jan Y. N., Jan L. Y. Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel. Nature. 1993 Aug 26;364(6440):802–806. doi: 10.1038/364802a0. [DOI] [PubMed] [Google Scholar]
  16. Martin P., Levy M. N., Matsuda Y. Fade of cardiac responses during tonic vagal stimulation. Am J Physiol. 1982 Aug;243(2):H219–H225. doi: 10.1152/ajpheart.1982.243.2.H219. [DOI] [PubMed] [Google Scholar]
  17. Mubagwa K., Carmeliet E. Effects of acetylcholine on electrophysiological properties of rabbit cardiac Purkinje fibers. Circ Res. 1983 Dec;53(6):740–751. doi: 10.1161/01.res.53.6.740. [DOI] [PubMed] [Google Scholar]
  18. Reuveny E., Slesinger P. A., Inglese J., Morales J. M., Iñiguez-Lluhi J. A., Lefkowitz R. J., Bourne H. R., Jan Y. N., Jan L. Y. Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits. Nature. 1994 Jul 14;370(6485):143–146. doi: 10.1038/370143a0. [DOI] [PubMed] [Google Scholar]
  19. Shui Z., Boyett M. R., Zang W. J., Haga T., Kameyama K. Receptor kinase-dependent desensitization of the muscarinic K+ current in rat atrial cells. J Physiol. 1995 Sep 1;487(Pt 2):359–366. doi: 10.1113/jphysiol.1995.sp020885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ten Eick R., Nawrath H., McDonald T. F., Trautwein W. On the mechanism of the negative inotropic effect of acetylcholine. Pflugers Arch. 1976 Feb 24;361(3):207–213. doi: 10.1007/BF00587284. [DOI] [PubMed] [Google Scholar]
  21. Trautwein W., Hescheler J. Regulation of cardiac L-type calcium current by phosphorylation and G proteins. Annu Rev Physiol. 1990;52:257–274. doi: 10.1146/annurev.ph.52.030190.001353. [DOI] [PubMed] [Google Scholar]
  22. Wang Y. G., Lipsius S. L. Acetylcholine potentiates acetylcholine-induced increases in K+ current in cat atrial myocytes. Am J Physiol. 1995 Mar;268(3 Pt 2):H1313–H1321. doi: 10.1152/ajpheart.1995.268.3.H1313. [DOI] [PubMed] [Google Scholar]
  23. Watson N., Linder M. E., Druey K. M., Kehrl J. H., Blumer K. J. RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits. Nature. 1996 Sep 12;383(6596):172–175. doi: 10.1038/383172a0. [DOI] [PubMed] [Google Scholar]
  24. Zang W. J., Yu X. J., Honjo H., Kirby M. S., Boyett M. R. On the role of G protein activation and phosphorylation in desensitization to acetylcholine in guinea-pig atrial cells. J Physiol. 1993 May;464:649–679. doi: 10.1113/jphysiol.1993.sp019656. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES