description): Cardiac gap junctions are vital to conduction of the cardiac action potential since they form a low resistance intercellular pathway for ionic current flow between cardiac cells. The mechanism(s) for ion permeation and the connexin protein domain that forms the hydrophilic pore remains unknown. The main goal of this research project is to determine how cations and anions permeate through different connexin channel pores and identify the protein domains that form the ionic permeation pathway. The differential ionic permeability of connexin-specific channels will be determined by varying the concentration and cation/anion composition of permeant ionic salts. Relative ionic permeability ratios will be determined from the diffusion potential developed under asymmetric (biionic) salt conditions and the concentration-dependence or counterion-dependence of these values will distinguish between three different hypotheses for cation and anion permeation (electrostatic forces, countercurrent flux, cotransport of ions) through a pore. The mechanism of ionic blockade by tetraalkylammonium (TAA) and polyamines within the connexin pore will be determined as a measure of the number of sites required and the fraction of the voltage field sensed by the blocking ions. In addition, the conductance and ionic permeability properties of heterotypic connexin channels will be determined. Chimeric and site-directed mutant connexins from two connexins of different conductances and ionic permeabilities will be studied to determine which molecular domain(s) form the channel pore.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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Upstate Medical University
Schools of Medicine
United States
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Zou, Juan; Salarian, Mani; Chen, Yanyi et al. (2017) Direct visualization of interaction between calmodulin and connexin45. Biochem J 474:4035-4051
Reddish, Florence N; Miller, Cassandra L; Gorkhali, Rakshya et al. (2017) Calcium Dynamics Mediated by the Endoplasmic/Sarcoplasmic Reticulum and Related Diseases. Int J Mol Sci 18:
Zou, Juan; Jiang, Jason Y; Yang, Jenny J (2017) Molecular Basis for Modulation of Metabotropic Glutamate Receptors and Their Drug Actions by Extracellular Ca2. Int J Mol Sci 18:
Turaga, Ravi Chakra; Yin, Lu; Yang, Jenny J et al. (2016) Rational design of a protein that binds integrin ?v?3 outside the ligand binding site. Nat Commun 7:11675
Veenstra, Richard D (2016) Establishment of the Dual Whole Cell Recording Patch Clamp Configuration for the Measurement of Gap Junction Conductance. Methods Mol Biol 1437:213-31
Xu, Qin; Lin, Xianming; Matiukas, Arvydas et al. (2016) Specificity of the connexin W3/4 locus for functional gap junction formation. Channels (Austin) 10:453-65
Hsieh, Ying-Hsin; Zou, Juan; Jin, Jin-Shan et al. (2015) Monitoring channel activities of proteoliposomes with SecA and Cx26 gap junction in single oocytes. Anal Biochem 480:58-66
Lin, Xianming; Xu, Qin; Veenstra, Richard D (2014) Functional formation of heterotypic gap junction channels by connexins-40 and -43. Channels (Austin) 8:433-43
Zou, Juan; Salarian, Mani; Chen, Yanyi et al. (2014) Gap junction regulation by calmodulin. FEBS Lett 588:1430-8
Patel, Dakshesh; Gemel, Joanna; Xu, Qin et al. (2014) Atrial fibrillation-associated connexin40 mutants make hemichannels and synergistically form gap junction channels with novel properties. FEBS Lett 588:1458-64

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