title: Ovariectomy-induced reductions in endothelial SK3 channel activity and endothelium-dependent vasorelaxation in murine mesenteric arteries.
abstract: Mesenteric artery endothelium expresses both small (SK3)- and intermediate (IK1)-conductance Ca(2+)-activated K(+) (KCa) channels whose activity modulates vascular tone via endothelium-dependent hyperpolarization (EDH). Two other major endothelium-dependent vasodilation pathways utilize nitric oxide (NO) and prostacyclin (PGI2). To examine how ovariectomy (ovx) affects the basal activity and acetylcholine (ACh)-induced activity of each of these three pathways to vasorelaxation, we used wire myograph and electrophysiological recordings. The results from functional studies using isolated murine mesenteric arteries show that ovx reduces ACh-induced endothelium-dependent vasodilation due to decreased EDH and NO contributions, although the contribution of PGI2 is upregulated. Both endothelial SK3 and IK1 channels are functionally coupled to TRPV4 (transient receptor potential, vanilloid type 4) channels: the activation of TRPV4 channels activates SK3 and IK1 channels, leading to EDH-mediated vascular relaxation. The decreased EDH-mediated vasorelaxation in ovx vessels is due to reduced SK3 channel contribution to the pathway. Further, whole-cell recordings using dispersed endothelial cells also show reduced SK3 current density in ovx endothelial cells. Consequently, activation of TRPV4 channels induces smaller changes in whole-cell current density. Thus, ovariectomy leads to a reduction in endothelial SK3 channel activity thereby reducing the SK3 contribution to EDH vasorelaxation.
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, Alabama, United States of America.
authors.forename: Fui C
authors.initials: FC
authors.lastname: Yap
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, Alabama, United States of America.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Taylor
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, Alabama, United States of America.
authors.forename: Mike T
authors.initials: MT
authors.lastname: Lin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008638:Mesenteric Arteries / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496900:Kcnn3 protein, mouse; D051640:Small-Conductance Calcium-Activated Potassium Channels; D009569:Nitric Oxide; D000109:Acetylcholine
references.citation: PLoS One. 2014 Mar 14;9(3):e92013
references.pmid: 24632741
references.citation: Clin Sci (Lond). 2009 Jul 16;117(4):139-55
references.pmid: 19601928
references.citation: J Biol Chem. 2003 Jul 18;278(29):27208-15
references.pmid: 12732636
references.citation: Fertil Steril. 2004 Aug;82(2):391-7
references.pmid: 15302289
references.citation: J Biol Chem. 1998 Aug 28;273(35):22267-71
references.pmid: 9712842
references.citation: Cardiovasc Res. 2004 Nov 1;64(2):234-42
references.pmid: 15485682
references.citation: Circulation. 2009 May 5;119(17):2323-32
references.pmid: 19380617
references.citation: Br J Pharmacol. 2007 Jun;151(3):332-40
references.pmid: 17450174
references.citation: Am J Physiol Cell Physiol. 2012 Apr 15;302(8):C1226-42
references.pmid: 22277756
references.citation: Circ Res. 2003 Jul 25;93(2):124-31
references.pmid: 12805243
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Feb;286(2):R233-49
references.pmid: 14707008
references.citation: J Appl Physiol (1985). 2001 Oct;91(4):1868-83
references.pmid: 11568174
references.citation: Cardiovasc Res. 2002 Feb 15;53(3):688-708
references.pmid: 11861040
references.citation: Circulation. 2008 Feb 26;117(8):1065-74
references.pmid: 18268148
references.citation: J Anat. 2006 Nov;209(5):689-98
references.pmid: 17062025
references.citation: J Cardiovasc Pharmacol. 1996 Nov;28(5):703-11
references.pmid: 8945685
references.citation: Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1793-800
references.pmid: 14704224
references.citation: Curr Hypertens Rep. 2006 Apr;8(1):84-9
references.pmid: 16600164
references.citation: J Physiol. 2004 Dec 1;561(Pt 2):535-45
references.pmid: 15388783
references.citation: Am J Physiol Heart Circ Physiol. 2001 Sep;281(3):H1327-33
references.pmid: 11514304
references.citation: Br J Pharmacol. 2003 Feb;138(4):594-601
references.pmid: 12598413
references.citation: FASEB J. 2011 Nov;25(11):3938-48
references.pmid: 21828287
references.citation: Ann Intern Med. 1976 Oct;85(4):447-52
references.pmid: 970770
references.citation: J Physiol. 2003 Nov 15;553(Pt 1):183-9
references.pmid: 14555724
references.citation: Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E503-12
references.pmid: 19126786
references.citation: Science. 2012 May 4;336(6081):597-601
references.pmid: 22556255
references.citation: Physiol Rep. 2013 Oct;1(5):e00121
references.pmid: 24303188
references.citation: Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2275-84
references.pmid: 17209000
references.citation: Am J Physiol Cell Physiol. 2012 Aug 1;303(3):C318-27
references.pmid: 22621787
references.citation: Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H701-9
references.pmid: 12689856
references.citation: BMJ. 2012 Feb 16;344:e763
references.pmid: 22344303
references.citation: J Hum Hypertens. 1989 Dec;3(6):427-33
references.pmid: 2607517
references.citation: Br J Pharmacol. 2011 Jan;162(2):365-77
references.pmid: 20840539
references.citation: Br J Pharmacol. 2005 Jan;144(2):178-89
references.pmid: 15655506
references.citation: Mol Cell Endocrinol. 2013 Mar 10;367(1-2):85-97
references.pmid: 23305677
references.citation: Eur Heart J. 1997 Nov;18 Suppl E:E19-29
references.pmid: 9402468
references.citation: N Engl J Med. 2009 Feb 5;360(6):573-87
references.pmid: 19196674
references.citation: Biochem Biophys Res Commun. 2003 Apr 4;303(2):660-8
references.pmid: 12659870
references.citation: Circulation. 2009 Sep 29;120(13):1266-86
references.pmid: 19786641
references.citation: J Am Soc Nephrol. 2012 Jul;23(7):1172-80
references.pmid: 22518003
references.citation: J Cardiovasc Pharmacol. 2005 Oct;46(4):438-44
references.pmid: 16160594
references.citation: Stroke. 2000 Jan;31(1):161-8
references.pmid: 10625733
references.citation: Br J Pharmacol. 2001 Mar;132(5):1035-46
references.pmid: 11226134
references.citation: Circ Res. 2006 Sep 1;99(5):537-44
references.pmid: 16873714
references.citation: Am J Physiol Cell Physiol. 2007 Jul;293(1):C458-67
references.pmid: 17459950
references.citation: Am J Physiol. 1998 Jul;275(1):H292-300
references.pmid: 9688926
references.citation: JAMA. 1991 Apr 10;265(14):1861-7
references.pmid: 2005736
references.citation: Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):127-35
references.pmid: 24177326
references.citation: Br J Pharmacol. 1996 Nov;119(5):959-64
references.pmid: 8922746
references.citation: Endocrinology. 2002 Mar;143(3):1097-107
references.pmid: 11861537