J Physiol Boston Smyposia
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Physiology in Press

First published online on April 5, 2002.
 Copyright © 2002 by The Physiological Society
This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
541/2/435    most recent
2002.018515v1
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Colecraft, H. M.
Right arrow Articles by Yue, T.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Colecraft, H. M.
Right arrow Articles by Yue, T.

Received February 5, 2002
Accepted after revision March 5, 2002

Novel functional properties of Ca2+ channel ß subunits revealed by their expression in adult rat heart cells

Henry M. Colecraft1*, Badr Alseikhan2, Shoji X. Takahashi2, Dipayan Chaudhuri3, Scott Mittman4, Vasan Yegnasubramanian2, Rebecca S. Alvania2, David C. Johns5, Eduardo Marbán6, and T. Yue7

1 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Traylor Building, Room 710A, 720 Rutland Avenue, Baltimore, MD 21205, USA
2 Program in Molecular and Cellular Systems Physiology, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Traylor Building, Room 710A, 720 Rutland Avenue, Baltimore, MD 21205, USA
3 Program in Molecular and Cellular Systems Physiology, Departments of Biomedical Engineering and Neuroscience, Johns Hopkins University School of Medicine, Traylor Building, Room 710A, 720 Rutland Avenue, Baltimore, MD 21205, USA
4 Program in Molecular and Cellular Systems Physiology, Department of Anesthesiology and Physiology, Johns Hopkins University School of Medicine, Traylor Building, Room 710A, 720 Rutland Avenue, Baltimore, MD 21205, USA
5 Program in Molecular and Cellular Systems Physiology, Departments of Neurosurgery, Johns Hopkins University School of Medicine, Traylor Building, Room 710A, 720 Rutland Avenue, Baltimore, MD 21205, USA
6 Program in Molecular and Cellular Systems Physiology, The Institute for Molecular Cardiobiology and The Division of Cardiology, Johns Hopkins University School of Medicine, Traylor Building, Room 710A, 720 Rutland Avenue, Baltimore, MD 21205, USA
7 Program in Molecular and Cellular Systems Physiology, Departments of * Biomedical Engineering and Neuroscience, Johns Hopkins University School of Medicine, Traylor Building, Room 710A, 720 Rutland Avenue, Baltimore, MD 21205, USA

* To whom correspondence should be addressed. E-mail: hcolecra{at}bme.jhu.edu.

Recombinant adenoviruses were used to overexpress green fluorescent protein (GFP)-fused auxiliary Ca2+ channel ß subunits (ß1-ß4) in cultured adult rat heart cells, to explore new dimensions of ß subunit functions in vivo. Distinct ß-GFP subunits distributed differentially between the surface sarcolemma, transverse elements, and nucleus in single heart cells. All ß-GFP subunits increased the native cardiac whole-cell L-type Ca2+ channel current density, but produced distinctive effects on channel inactivation kinetics. The degree of enhancement of whole-cell current density was non-uniform between ß subunits, with a rank order of potency ß2a ~ ß4 > ß1b > ß3. For each ß subunit, the increase in L-type current density was accompanied by a correlative increase in the maximal gating charge (Qmax) moved with depolarization. However, ß subunits produced characteristic effects on single L-type channel gating, resulting in divergent effects on channel open probability (Po). Quantitative analysis and modelling of single-channel data provided a kinetic signature for each channel type. Spurred on by ambiguities regarding the molecular identity of the actual endogenous cardiac L-type channel ß subunit, we cloned a new rat ß2 splice variant, ß2b, from heart using 5â rapid amplification of cDNA ends (RACE) PCR. By contrast with ß2a, expression of ß2b in heart cells yielded channels with a microscopic gating signature virtually identical to that of native unmodified channels. Our results provide novel insights into ß subunit functions that are unattainable in traditional heterologous expression studies, and also provide new perspectives on the molecular identity of the ß subunit component of cardiac L-type Ca2+ channels. Overall, the work establishes a powerful experimental protocol to explore novel functions of ion channel subunits in their native environments.




This article has been cited by other articles:


Home page
 Physiol. GenomicsHome page
A. M. Ebert, C. A. McAnelly, A. V. Handschy, R. L. Mueller, W. A. Horne, and D. M. Garrity
Genomic organization, expression, and phylogenetic analysis of Ca2+ channel {beta}4 genes in 13 vertebrate species
Physiol Genomics, October 8, 2008; 35(2): 133 - 144.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Ravindran, Q. Z. Lao, J. B. Harry, P. Abrahimi, E. Kobrinsky, and N. M. Soldatov
Calmodulin-dependent gating of Cav1.2 calcium channels in the absence of Cav{beta} subunits
PNAS, June 10, 2008; 105(23): 8154 - 8159.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Q. Z. Lao, E. Kobrinsky, J. B. Harry, A. Ravindran, and N. M. Soldatov
New Determinant for the CaV{beta}2 Subunit Modulation of the CaV1.2 Calcium Channel
J. Biol. Chem., June 6, 2008; 283(23): 15577 - 15588.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. Miriyala, T. Nguyen, D. T. Yue, and H. M. Colecraft
Role of CaV{beta} Subunits, and Lack of Functional Reserve, in Protein Kinase A Modulation of Cardiac CaV1.2 Channels
Circ. Res., April 11, 2008; 102(7): e54 - e64.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
V. Gudzenko, Y. Shiferaw, N. Savalli, R. Vyas, J. N. Weiss, and R. Olcese
Influence of channel subunit composition on L-type Ca2+ current kinetics and cardiac wave stability
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1805 - H1815.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
L.-l. He, Y. Zhang, Y.-h. Chen, Y. Yamada, and J. Yang
Functional Modularity of the {beta}-Subunit of Voltage-Gated Ca2+ Channels
Biophys. J., August 1, 2007; 93(3): 834 - 845.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
E. Cingolani, G. A. Ramirez Correa, E. Kizana, M. Murata, H. C. Cho, and E. Marban
Gene Therapy to Inhibit the Calcium Channel {beta} Subunit: Physiological Consequences and Pathophysiological Effects in Models of Cardiac Hypertrophy
Circ. Res., July 20, 2007; 101(2): 166 - 175.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. Herzig, I. F. Y. Khan, D. Grundemann, J. Matthes, A. Ludwig, G. Michels, U. C. Hoppe, D. Chaudhuri, A. Schwartz, D. T. Yue, et al.
Mechanism of Cav1.2 channel modulation by the amino terminus of cardiac {beta}2-subunits
FASEB J, May 1, 2007; 21(7): 1527 - 1538.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
H. E. D. J. ter Keurs and P. A. Boyden
Calcium and Arrhythmogenesis
Physiol Rev, April 1, 2007; 87(2): 457 - 506.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
E. Schroder, J. Magyar, D. Burgess, D. Andres, and J. Satin
Chronic verapamil treatment remodels ICa,L in mouse ventricle
Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1906 - H1916.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. E. Anderson
Multiple downstream proarrhythmic targets for calmodulin kinase II: Moving beyond an ion channel-centric focus
Cardiovasc Res, March 1, 2007; 73(4): 657 - 666.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. R. Smith, L. Barile, H. C. Cho, M. K. Leppo, J. M. Hare, E. Messina, A. Giacomello, M. R. Abraham, and E. Marban
Regenerative Potential of Cardiosphere-Derived Cells Expanded From Percutaneous Endomyocardial Biopsy Specimens
Circulation, February 20, 2007; 115(7): 896 - 908.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
H. Haase
Ahnak, a new player in {beta}-adrenergic regulation of the cardiac L-type Ca2+ channel
Cardiovasc Res, January 1, 2007; 73(1): 19 - 25.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S.-N. Yang and P.-O. Berggren
The Role of Voltage-Gated Calcium Channels in Pancreatic {beta}-Cell Physiology and Pathophysiology
Endocr. Rev., October 1, 2006; 27(6): 621 - 676.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
J. T. Hulme, V. Yarov-Yarovoy, T. W.-C. Lin, T. Scheuer, and W. A. Catterall
Autoinhibitory control of the CaV1.2 channel by its proteolytically processed distal C-terminal domain
J. Physiol., October 1, 2006; 576(1): 87 - 102.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. M. Crump, R. N. Correll, E. A. Schroder, W. C. Lester, B. S. Finlin, D. A. Andres, and J. Satin
L-type calcium channel {alpha}-subunit and protein kinase inhibitors modulate Rem-mediated regulation of current
Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1959 - H1971.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
N. Kanevsky and N. Dascal
Regulation of Maximal Open Probability Is a Separable Function of Cav{beta} Subunit in L-type Ca2+ Channel, Dependent on NH2 Terminus of {alpha}1C (Cav1.2{alpha})
J. Gen. Physiol., June 26, 2006; 128(1): 15 - 36.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
A. N. Ganesan, C. Maack, D. C. Johns, A. Sidor, and B. O'Rourke
{beta}-Adrenergic Stimulation of L-type Ca2+ Channels in Cardiac Myocytes Requires the Distal Carboxyl Terminus of {alpha}1C but Not Serine 1928
Circ. Res., February 3, 2006; 98(2): e11 - e18.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
H. Haase, J. Alvarez, D. Petzhold, A. Doller, J. Behlke, J. Erdmann, R. Hetzer, V. Regitz-Zagrosek, G. Vassort, and I. Morano
Ahnak is critical for cardiac Ca(v)1.2 calcium channel function and its {beta}-adrenergic regulation
FASEB J, December 1, 2005; 19(14): 1969 - 1977.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
M. C. Garcia, E. Carrillo, J. M. Galindo, A. Hernandez, J. A. Copello, M. Fill, and J. A. Sanchez
Short-Term Regulation of Excitation-Contraction Coupling by the {beta}1a Subunit in Adult Mouse Skeletal Muscle
Biophys. J., December 1, 2005; 89(6): 3976 - 3984.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
X. Chen, X. Zhang, H. Kubo, D. M. Harris, G. D. Mills, J. Moyer, R. Berretta, S. T. Potts, J. D. Marsh, and S. R. Houser
Ca2+ Influx-Induced Sarcoplasmic Reticulum Ca2+ Overload Causes Mitochondrial-Dependent Apoptosis in Ventricular Myocytes
Circ. Res., November 11, 2005; 97(10): 1009 - 1017.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. M. Nerbonne and R. S. Kass
Molecular Physiology of Cardiac Repolarization
Physiol Rev, October 1, 2005; 85(4): 1205 - 1253.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
S. X. Takahashi, J. Miriyala, L. H. Tay, D. T. Yue, and H. M. Colecraft
A CaV{beta} SH3/Guanylate Kinase Domain Interaction Regulates Multiple Properties of Voltage-gated Ca2+ Channels
J. Gen. Physiol., September 26, 2005; 126(4): 365 - 377.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Dalton, S. X Takahashi, J. Miriyala, and H. M Colecraft
A single CaV{beta} can reconstitute both trafficking and macroscopic conductance of voltage-dependent calcium channels
J. Physiol., September 15, 2005; 567(3): 757 - 769.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. Splawski, K. W. Timothy, N. Decher, P. Kumar, F. B. Sachse, A. H. Beggs, M. C. Sanguinetti, and M. T. Keating
Inaugural Article: Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations
PNAS, June 7, 2005; 102(23): 8089 - 8096.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
R. M. Cohen, J. D. Foell, R. C. Balijepalli, V. Shah, J. W. Hell, and T. J. Kamp
Unique modulation of L-type Ca2+ channels by short auxiliary {beta}1d subunit present in cardiac muscle
Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2363 - H2374.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Kobrinsky, S. Tiwari, V. A. Maltsev, J. B. Harry, E. Lakatta, D. R. Abernethy, and N. M. Soldatov
Differential Role of the {alpha}1C Subunit Tails in Regulation of the Cav1.2 Channel by Membrane Potential, {beta} Subunits, and Ca2+ Ions
J. Biol. Chem., April 1, 2005; 280(13): 12474 - 12485.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. B. Harry, E. Kobrinsky, D. R. Abernethy, and N. M. Soldatov
New Short Splice Variants of the Human Cardiac Cav{beta}2 Subunit: REDEFINING THE MAJOR FUNCTIONAL MOTIFS IMPLEMENTED IN MODULATION OF THE Cav1.2 CHANNEL
J. Biol. Chem., November 5, 2004; 279(45): 46367 - 46372.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
S. Luvisetto, T. Fellin, M. Spagnolo, B. Hivert, P. F. Brust, M. M. Harpold, K. A. Stauderman, M. E. Williams, and D. Pietrobon
Modal Gating of Human CaV2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by {beta} Subunits
J. Gen. Physiol., October 25, 2004; 124(5): 445 - 461.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
E. Kobrinsky, K. J. F. Kepplinger, A. Yu, J. B. Harry, H. Kahr, C. Romanin, D. R. Abernethy, and N. M. Soldatov
Voltage-Gated Rearrangements Associated with Differential {beta}-Subunit Modulation of the L-Type Ca2+ Channel Inactivation
Biophys. J., August 1, 2004; 87(2): 844 - 857.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. X. Takahashi, J. Miriyala, and H. M. Colecraft
Membrane-associated guanylate kinase-like properties of {beta}-subunits required for modulation of voltage-dependent Ca2+ channels
PNAS, May 4, 2004; 101(18): 7193 - 7198.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
J. D. Foell, R. C. Balijepalli, B. P. Delisle, A. M. R. Yunker, S. L. Robia, J. W. Walker, M. W. McEnery, C. T. January, and T. J. Kamp
Molecular heterogeneity of calcium channel {beta}-subunits in canine and human heart: evidence for differential subcellular localization
Physiol Genomics, April 13, 2004; 17(2): 183 - 200.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Alvarez, J. Hamplova, A. Hohaus, I. Morano, H. Haase, and G. Vassort
Calcium Current in Rat Cardiomyocytes Is Modulated by the Carboxyl-terminal Ahnak Domain
J. Biol. Chem., March 26, 2004; 279(13): 12456 - 12461.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. T. Hulme, T. W.-C. Lin, R. E. Westenbroek, T. Scheuer, and W. A. Catterall
{beta}-Adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15
PNAS, October 28, 2003; 100(22): 13093 - 13098.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. M. Schjott, S.-C. Hsu, and M. R. Plummer
The Neuronal {beta}4 Subunit Increases the Unitary Conductance of L-type Voltage-gated Calcium Channels in PC12 Cells
J. Biol. Chem., September 5, 2003; 278(36): 33936 - 33942.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Hullin, I. F. Y. Khan, S. Wirtz, P. Mohacsi, G. Varadi, A. Schwartz, and S. Herzig
Cardiac L-type Calcium Channel {beta}-Subunits Expressed in Human Heart Have Differential Effects on Single Channel Characteristics
J. Biol. Chem., June 6, 2003; 278(24): 21623 - 21630.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
S. X. Takahashi, S. Mittman, and H. M. Colecraft
Distinctive Modulatory Effects of Five Human Auxiliary {beta}2 Subunit Splice Variants on L-Type Calcium Channel Gating
Biophys. J., May 1, 2003; 84(5): 3007 - 3021.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. A. Alseikhan, C. D. DeMaria, H. M. Colecraft, and D. T. Yue
Engineered calmodulins reveal the unexpected eminence of Ca2+ channel inactivation in controlling heart excitation
PNAS, December 24, 2002; 99(26): 17185 - 17190.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2002 The Physiological Society.