Circulation Research. 2003;93:965-971
Published online before print October 9, 2003, doi: 10.1161/01.RES.0000100068.43006.36
Published online before print October 9, 2003, doi: 10.1161/01.RES.0000100068.43006.36
© 2003 American Heart Association, Inc.
Cellular Biology |
Downregulation of the BK Channel ß1 Subunit in Genetic Hypertension
From the Department of Physiology and Biophysics, University of Washington, Seattle, Wash.
Correspondence to L.F. Santana, Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195. E-mail santana{at}u.washington.edu
The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca2+ release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca2+ sparks) activate large-conductance, Ca2+-sensitive K+ (BK) channels. Ca2+ sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca2+ sparks and BK channel function in Wistar-Kyoto (WKY) rats with borderline hypertension and in spontaneously hypertensive rats (SHR), a widely used genetic model of severe hypertension. We found that the amplitude of spontaneous BK currents in WKY and SHR cells were smaller than in normotensive cells even though Ca2+ sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca2+ than normotensive cells. Our data indicate that decreased expression of the BK channel ß1 subunit underlies the lower Ca2+ sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the ß1 subunit during genetic borderline and severe hypertension reduced BK channel activity by decreasing the sensitivity of these channels to physiological changes in Ca2+. These results support the view that changes in the molecular composition of BK channels may be a fundamental event contributing to the development of vascular dysfunction during hypertension.
Key Words: Ca2+ sparks • ryanodine receptors • sarcoplasmic reticulum • iberiotoxin
This article has been cited by other articles:
 |
|
 |
|
  N. J. Rusch BK channels in cardiovascular disease: a complex story of channel dysregulation Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1580 - H1582. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhu, D. D. Browning, R. E. White, D. Fulton, and S. A. Barman Mutation of protein kinase C phosphorylation site S1076 on {alpha}-subunits affects BKCa channel activity in HEK-293 cells Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L758 - L766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Tobin, B. K. Joseph, H. N. Al-Kindi, S. Albarwani, J. A. Madden, L. T. Nemetz, N. J. Rusch, and S. W. Rhee Loss of cerebrovascular Shaker-type K+ channels: a shared vasodilator defect of genetic and renal hypertensive rats Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H293 - H303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Moreno-Dominguez, P. Cidad, E. Miguel-Velado, J. R. Lopez-Lopez, and M. T. Perez-Garcia De novo expression of Kv6.3 contributes to changes in vascular smooth muscle cell excitability in a hypertensive mice strain J. Physiol., February 1, 2009; 587(3): 625 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cheng and W. J. Lederer Calcium Sparks Physiol Rev, October 1, 2008; 88(4): 1491 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bao, L. M. Lifshitz, R. A. Tuft, K. Bellve, K. E. Fogarty, and R. ZhuGe A Close Association of RyRs with Highly Dense Clusters of Ca2+-activated Cl- Channels Underlies the Activation of STICs by Ca2+ Sparks in Mouse Airway Smooth Muscle J. Gen. Physiol., July 1, 2008; 132(1): 145 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Navedo, M. Nieves-Cintron, G. C. Amberg, C. Yuan, V. S. Votaw, W. J. Lederer, G. S. McKnight, and L. F. Santana AKAP150 Is Required for Stuttering Persistent Ca2+ Sparklets and Angiotensin II-Induced Hypertension Circ. Res., February 1, 2008; 102(2): e1 - e11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-L. Ambroisine, J. Favre, P. Oliviero, C. Rodriguez, J. Gao, C. Thuillez, J.-L. Samuel, V. Richard, and C. Delcayre Aldosterone-Induced Coronary Dysfunction in Transgenic Mice Involves the Calcium-Activated Potassium (BKCa) Channels of Vascular Smooth Muscle Cells Circulation, November 20, 2007; 116(21): 2435 - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Navedo, G. C. Amberg, R. E. Westenbroek, M. J. Sinnegger-Brauns, W. A. Catterall, J. Striessnig, and L. F. Santana Cav1.3 channels produce persistent calcium sparklets, but Cav1.2 channels are responsible for sparklets in mouse arterial smooth muscle Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1359 - H1370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Clapp and N. N. Orie Stoking Up BKCa Channels in Hemorrhagic Shock: Which Channel Subunit Is Really Fueling the Fire? Circ. Res., August 31, 2007; 101(5): 436 - 438. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bolognesi, D. Sacerdoti, A. Piva, M. Di Pascoli, F. Zampieri, S. Quarta, R. Motterlini, P. Angeli, C. Merkel, and A. Gatta Carbon Monoxide-Mediated Activation of Large-Conductance Calcium-Activated Potassium Channels Contributes to Mesenteric Vasodilatation in Cirrhotic Rats J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 187 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Amberg, M. F. Navedo, M. Nieves-Cintron, J. D. Molkentin, and L. F. Santana Calcium sparklets regulate local and global calcium in murine arterial smooth muscle J. Physiol., February 15, 2007; 579(1): 187 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nieves-Cintron, G. C. Amberg, C. B. Nichols, J. D. Molkentin, and L. F. Santana Activation of NFATc3 Down-regulates the beta1 Subunit of Large Conductance, Calcium-activated K+ Channels in Arterial Smooth Muscle and Contributes to Hypertension J. Biol. Chem., February 2, 2007; 282(5): 3231 - 3240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cogolludo, G. Frazziano, A. M. Briones, L. Cobeno, L. Moreno, F. Lodi, M. Salaices, J. Tamargo, and F. Perez-Vizcaino The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of H2O2. Role in vasodilatation Cardiovasc Res, January 15, 2007; 73(2): 424 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kiyoshi, D. Yamazaki, S. Ohya, M. Kitsukawa, K. Muraki, S.-y. Saito, Y. Ohizumi, and Y. Imaizumi Molecular and electrophysiological characteristics of K+ conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2723 - H2734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xu, W. F. Jackson, G. D. Fink, and J. J. Galligan Activation of Potassium Channels by Tempol in Arterial Smooth Muscle Cells From Normotensive and Deoxycorticosterone Acetate-Salt Hypertensive Rats Hypertension, December 1, 2006; 48(6): 1080 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Amberg and L. F. Santana Kv2 channels oppose myogenic constriction of rat cerebral arteries Am J Physiol Cell Physiol, August 1, 2006; 291(2): C348 - C356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Navedo, G. C. Amberg, M. Nieves, J. D. Molkentin, and L. F. Santana Mechanisms Underlying Heterogeneous Ca2+ Sparklet Activity in Arterial Smooth Muscle J. Gen. Physiol., May 30, 2006; 127(6): 611 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Resnik, J. Herron, R. Fu, D. D. Ivy, and D. N. Cornfield Oxygen tension modulates the expression of pulmonary vascular BKCa channel {alpha}- and beta-subunits Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L761 - L768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Amberg, M. F. Navedo, and L. F. Santana On the Loose: Uncaging Ca2+-induced Ca2+ Release in Smooth Muscle J. Gen. Physiol., February 27, 2006; 127(3): 221 - 223. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ledoux, M. E. Werner, J. E. Brayden, and M. T. Nelson Calcium-Activated Potassium Channels and the Regulation of Vascular Tone Physiology, February 1, 2006; 21(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Nagar, X.-t. Liu, and C. R. Rosenfeld Estrogen regulates {beta}1-subunit expression in Ca2+-activated K+ channels in arteries from reproductive tissues Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1417 - H1427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Rosenfeld, T. Roy, K. DeSpain, and B. E. Cox Large-Conductance Ca2+-Dependent K+ Channels Regulate Basal Uteroplacental Blood Flow in Ovine Pregnancy Reproductive Sciences, September 1, 2005; 12(6): 402 - 408. [Abstract] [PDF]
|
|
|
|
|
|
I. N. Bratz, G. M. Dick, L. D. Partridge, and N. L. Kanagy Reduced molecular expression of K+ channel proteins in vascular smooth muscle from rats made hypertensive with N{omega}-nitro-L-arginine Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1277 - H1283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. N. Bratz, A. N. Swafford Jr., N. L. Kanagy, and G. M. Dick Reduced functional expression of K+ channels in vascular smooth muscle cells from rats made hypertensive with N{omega}-nitro-L-arginine Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1284 - H1290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Navarro-Antolin, K. L. Levitsky, E. Calderon, A. Ordonez, and J. Lopez-Barneo Decreased Expression of Maxi-K+ Channel {beta}1-Subunit and Altered Vasoregulation in Hypoxia Circulation, August 30, 2005; 112(9): 1309 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Navedo, G. C. Amberg, V. S. Votaw, and L. F. Santana Constitutively active L-type Ca2+ channels PNAS, August 2, 2005; 102(31): 11112 - 11117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sausbier, C. Arntz, I. Bucurenciu, H. Zhao, X.-B. Zhou, U. Sausbier, S. Feil, S. Kamm, K. Essin, C. A. Sailer, et al. Elevated Blood Pressure Linked to Primary Hyperaldosteronism and Impaired Vasodilation in BK Channel-Deficient Mice Circulation, July 5, 2005; 112(1): 60 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Loewen and G. W. Forsyth Structure and Function of CLCA Proteins Physiol Rev, July 1, 2005; 85(3): 1061 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Perez Dual Effect of Tamoxifen on Arterial KCa Channels Does Not Depend on the Presence of the {beta}1 Subunit J. Biol. Chem., June 10, 2005; 280(23): 21739 - 21747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Kurjiaka, S. B. Bender, D. D. Nye, W. B. Wiehler, and D. G. Welsh Hypertension attenuates cell-to-cell communication in hamster retractor muscle feed arteries Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H861 - H870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Amberg, C. F. Rossow, M. F. Navedo, and L. F. Santana NFATc3 Regulates Kv2.1 Expression in Arterial Smooth Muscle J. Biol. Chem., November 5, 2004; 279(45): 47326 - 47334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Santarelli, J. Chen, S. H. Heinemann, and T. Hoshi The {beta}1 Subunit Enhances Oxidative Regulation of Large-Conductance Calcium-activated K+ Channels J. Gen. Physiol., September 27, 2004; 124(4): 357 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Clapp and R. I. Jabr The BK Channel: Protective or Detrimental in Genetic Hypertension? Circ. Res., November 14, 2003; 93(10): 893 - 895. [Full Text] [PDF]
|
|