Dissection of two Cx37-independent conducted vasodilator mechanisms by deletion of Cx40: electrotonic versus regenerative conduction.
Conduction of changes in diameter plays an important role in the coordination of peripheral vascular resistance and, thereby, in the control of arterial blood pressure. It is thought that conduction of vasomotor signals relies on the electrotonic spread of changes in membrane potential from a site of stimulation through gap junctions connecting the cells of the vessel wall. To explore this idea, we stimulated a short segment of mouse cremasteric arterioles with an application, via micropipette, of ACh, an endothelium-dependent vasodilator, or pinacidil, an ATP-sensitive K+ channel opener. Vasodilations were evaluated at the stimulation site (local) and at 500, 1,000, and 2,000 microm upstream. The vasodilator response evoked by direct arteriolar hyperpolarization induced by pinacidil decayed rapidly with distance, as expected for the passive spread of an electrical signal. Deletion of the gap junction proteins connexin37 or connexin40 did not alter the conduction of pinacidil-induced vasodilation. In contrast to pinacidil, the vasodilator response activated by ACh spread along the entire vessel without decrement. Although the ACh-induced conducted vasodilation was similar in wild-type and connexin37 knockout mice, deletion of connexin40 converted the nondecremental conducted response activated by ACh into one similar to that of pinacidil, with a decline in magnitude along the vessel length. These results suggest that ACh activates a mechanism of regenerative conduction of vasodilator responses. Connexin40 is essential for the ACh-activated regenerative vasodilator mechanism. However, neither connexin40 nor connexin37 is indispensable for the electrotonic spread of hyperpolarizing signals.
Figueroa
Xavier F
XF
Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. xfigueroa@bio.puc.cl
Duling
Brian R
BR
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001794:Blood Pressure; D017630:Connexins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D007150:Immunohistochemistry; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000098:blood supply*; D020110:Pinacidil / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D000109:Acetylcholine; D017630:Connexins; D054086:KATP Channels; D020110:Pinacidil; D014665:Vasodilator Agents; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
Histochem Cell Biol. 1999 Dec;112(6):479-86
10651100
Circ Res. 2007 Dec 7;101(12):1300-9
17932328
Kidney Int. 2007 Oct;72(7):814-22
17622273
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1371-83
17513486
Microcirculation. 2001 Feb;8(1):33-43
11296851
Am J Physiol. 1990 Jul;259(1 Pt 2):H14-22
1695818
Am J Physiol Heart Circ Physiol. 2000 Feb;278(2):H604-12
10666093
Am J Physiol Heart Circ Physiol. 2002 Sep;283(3):H996-H1004
12181129
Am J Physiol. 1995 Feb;268(2 Pt 2):H729-39
7864199
Circ Res. 2007 Mar 2;100(4):556-63
17255527
Acta Physiol Scand. 1999 Sep;167(1):11-21
10519972
Microcirculation. 2005 Jan-Feb;12(1):113-27
15804979
J Physiol. 1978 Jul;280:87-104
690942
Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H1199-205
16284228
J Appl Physiol (1985). 2004 Sep;97(3):1152-8
15169746
Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1319-28
16617135
Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H1832-9
10843879
Physiol Genomics. 2003 Apr 16;13(2):169-77
12700362
Circ Res. 2000 Mar 31;86(6):649-55
10747000
Circ Res. 2000 Jan 7-21;86(1):94-100
10625310
Hypertension. 2006 Nov;48(5):804-11
17015783
Curr Biol. 1998 Feb 26;8(5):295-8
9501069
Dev Biol. 2002 Nov 15;251(2):206-20
12435353
Am J Physiol. 1997 Nov;273(5):H2465-72
9374786
Circ Res. 2005 Aug 19;97(4):399-407
16037574
Physiol Rev. 2003 Oct;83(4):1359-400
14506308
Clin Exp Pharmacol Physiol. 2002 Jul;29(7):626-9
12060108
Circ Res. 1998 Sep 21;83(6):636-43
9742059
Trends Cell Biol. 1998 Dec;8(12):477-83
9861669
Am J Physiol Cell Physiol. 2003 Oct;285(4):C959-67
12826604
Cell Calcium. 2005 Jul;38(1):23-33
15907999
Circ Res. 2007 Dec 7;101(12):1292-9
17932322
J Cell Sci. 2003 Jun 1;116(Pt 11):2223-36
12697838
Clin Exp Pharmacol Physiol. 2002 Apr;29(4):312-6
11985542
J Physiol. 2004 May 1;556(Pt 3):887-903
14966304
J Vasc Res. 1996 Sep-Oct;33(5):380-5
8862143
Circ Res. 2005 Jul 8;97(1):44-51
15961721
Development. 2000 Oct;127(19):4179-93
10976050
Microcirculation. 2004 Jul-Aug;11(5):425-33
15280068
Circ Res. 2003 Apr 18;92(7):793-800
12637364
Am J Physiol. 1997 Mar;272(3 Pt 2):H1364-71
9087613
J Vasc Res. 2002 Mar-Apr;39(2):160-72
12011587
Physiology (Bethesda). 2004 Oct;19:277-84
15381756
Circ Res. 2003 Jul 11;93(1):61-8
12791708
Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H102-9
12063280
Am J Physiol. 1995 Dec;269(6 Pt 2):H2022-30
8594912
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9989-94
11481448