Display options
Cite
Berg T. Voltage-Sensitive K(+) Channels Inhibit Parasympathetic Ganglion Transmission and Vagal Control of Heart Rate in Hypertensive Rats. Front Neurol. 2015;6:260doi: 10.3389/fneur.2015.00260.
Berg, T. (2015). Voltage-Sensitive K(+) Channels Inhibit Parasympathetic Ganglion Transmission and Vagal Control of Heart Rate in Hypertensive Rats. Frontiers in neurology, 6260. https://doi.org/10.3389/fneur.2015.00260
Berg, Torill. "Voltage-Sensitive K(+) Channels Inhibit Parasympathetic Ganglion Transmission and Vagal Control of Heart Rate in Hypertensive Rats." Frontiers in neurology vol. 6 (2015): 260. doi: https://doi.org/10.3389/fneur.2015.00260
Berg T. Voltage-Sensitive K(+) Channels Inhibit Parasympathetic Ganglion Transmission and Vagal Control of Heart Rate in Hypertensive Rats. Front Neurol. 2015 Dec 08;6:260. doi: 10.3389/fneur.2015.00260. eCollection 2015. PMID: 26696959; PMCID: PMC4672051.
Copy Download .nbib Format: NLM
Share it on

Front Neurol. 2015 Dec 08;6:260. doi: 10.3389/fneur.2015.00260. eCollection 2015.

Voltage-Sensitive K(+) Channels Inhibit Parasympathetic Ganglion Transmission and Vagal Control of Heart Rate in Hypertensive Rats.

Frontiers in neurology

Torill Berg

Affiliations

  1. Division of Physiology, Department of Molecular Medicine, Institute for Basic Medical Sciences, University of Oslo , Oslo , Norway.

PMID: 26696959 PMCID: PMC4672051 DOI: 10.3389/fneur.2015.00260

Abstract

Parasympathetic withdrawal plays an important role in the autonomic dysfunctions in hypertension. Since hyperpolarizing, voltage-sensitive K(+) channels (K V) hamper transmitter release, elevated K V-activity may explain the disturbed vagal control of heart rate (HR) in hypertension. Here, the K V inhibitor 3,4-diaminopyridine was used to demonstrate the impact of K V on autonomic HR control. Cardiac output and HR were recorded by a flow probe on the ascending aorta in anesthetized, normotensive (WKY), and spontaneously hypertensive rats (SHR), and blood pressure by a femoral artery catheter. 3,4-diaminopyridine induced an initial bradycardia, which was greater in SHR than in WKY, followed by sustained tachycardia in both strains. The initial bradycardia was eliminated by acetylcholine synthesis inhibitor (hemicholinium-3) and nicotinic receptor antagonist/ganglion blocker (hexamethonium), and reversed to tachycardia by muscarinic receptor (mAchR) antagonist (atropine). The latter was abolished by sympatho-inhibition (reserpine). Reserpine also eliminated the late, 3,4-diaminopyridine-induced tachycardia in WKY, but induced a sustained atropine-sensitive bradycardia in SHR. Inhibition of the parasympathetic component with hemicholinium-3, hexamethonium, or atropine enhanced the late tachycardia in SHR, whereas hexamethonium reduced the tachycardia in WKY. In conclusion, 3,4-diaminopyridine-induced acetylcholine release, and thus enhanced parasympathetic ganglion transmission, with subsequent mAchR activation and bradycardia. 3,4-diaminopyridine also activated tachycardia, initially by enhancing sympathetic ganglion transmission, subsequently by activation of norepinephrine release from sympathetic nerve terminals. The 3,4-diaminopyridine-induced parasympathetic activation was stronger and more sustained in SHR, demonstrating an enhanced inhibitory control of K V on parasympathetic ganglion transmission. This enhanced K V activity may explain the dysfunctional vagal HR control in SHR.

Keywords: 3,4-diaminopyridine; acetylcholine release; heart rate; hypertension; norepinephrine release; parasympathetic ganglia; sympathetic ganglia; voltage-sensitive K+-channels

References

  1. J Vasc Res. 2014;51(6):447-57 - PubMed
  2. Naunyn Schmiedebergs Arch Pharmacol. 1987 Feb;335(2):216-8 - PubMed
  3. Eur J Pharmacol. 2002 Oct 11;452(3):325-37 - PubMed
  4. Circ Res. 2001 Nov 23;89(11):1038-44 - PubMed
  5. Hypertension. 2010 May;55(5):1224-30 - PubMed
  6. Am J Cardiol. 1987 Feb 1;59(4):256-62 - PubMed
  7. Eur J Pharmacol. 2003 Apr 18;466(3):301-10 - PubMed
  8. Am J Physiol Regul Integr Comp Physiol. 2005 Apr;288(4):R819-27 - PubMed
  9. Heart Fail Rev. 2011 Mar;16(2):129-35 - PubMed
  10. Nat Rev Neurosci. 2006 May;7(5):335-46 - PubMed
  11. Exp Physiol. 2011 Jul;96(7):611-22 - PubMed
  12. N Engl J Med. 1990 May 31;322(22):1561-6 - PubMed
  13. Br J Pharmacol. 1994 Dec;113(4):1567-73 - PubMed
  14. Curr Hypertens Rep. 2010 Jun;12(3):162-9 - PubMed
  15. Circulation. 2003 Aug 5;108(5):560-5 - PubMed
  16. Cardiovasc Drugs Ther. 1997 Jan;10(6):657-65 - PubMed
  17. Eur J Pharmacol. 1988 Jan 5;145(1):15-20 - PubMed
  18. Acta Physiol Scand. 1977 May;100(1):33-44 - PubMed
  19. Circ Res. 1996 Jun;78(6):1105-14 - PubMed
  20. J Vasc Res. 2009;46(1):25-35 - PubMed
  21. Front Neurol. 2012 Nov 08;3:160 - PubMed
  22. Front Neurol. 2011 Nov 23;2:71 - PubMed
  23. Front Physiol. 2014 Dec 19;5:499 - PubMed
  24. Am Heart J. 1994 Jan;127(1):122-8 - PubMed
  25. J Am Coll Cardiol. 1991 Aug;18(2):464-72 - PubMed
  26. Curr Hypertens Rep. 2009 Jun;11(3):199-205 - PubMed
  27. Brain Res. 1984 Jun 18;304(1):166-9 - PubMed
  28. J Physiol. 2013 Sep 1;591(17):4073-85 - PubMed
  29. Lancet. 1998 Feb 14;351(9101):478-84 - PubMed
  30. Exp Physiol. 2003 May;88(3):315-27 - PubMed
  31. J Smooth Muscle Res. 2008 Apr;44(2):65-81 - PubMed
  32. Front Neurol. 2014 Apr 16;5:51 - PubMed
  33. J Pharmacol Exp Ther. 1997 Nov;283(2):574-80 - PubMed
  34. Naunyn Schmiedebergs Arch Pharmakol. 1971;270(4):419-27 - PubMed
  35. Br J Pharmacol. 1969 Jun;36(2):240-52 - PubMed
  36. Fed Proc. 1984 Aug;43(11):2598-602 - PubMed
  37. Biochem J. 1992 Feb 1;281 ( Pt 3):819-28 - PubMed
  38. Cardiovasc Res. 2005 Sep 1;67(4):736-44 - PubMed
  39. Vascul Pharmacol. 2002 Jan;38(1):13-23 - PubMed
  40. Br J Pharmacol. 1982 Oct;77(2):239-44 - PubMed
  41. J Auton Nerv Syst. 1988 Apr;22(3):221-8 - PubMed

Publication Types