Coupling of β-Adrenergic Receptors to Cardiac L-Type Ca2+ Channels

Yatani, Atsuko; Tajima, Yasuhiro; Green, Stuart A.

doi:10.1016/s0898-6568(98)00050-3

Cited by 17 publications

(2 citation statements)

References 17 publications

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“…For example, the MEAs and Ca 2+ transients were recorded from large cellular aggregates with a minimum of three days in culture whereas patch clamp recordings required single cells and cell pairs thereby requiring a lower cell density and a much shorter time in culture. These factors of cell density and time in culture appear crucial to the differentiation levels of the HL-1 cell line exemplified by the appearance of spontaneous contractions only occurring after days in culture [4],[20],[45].…”

Section: Discussionmentioning

confidence: 99%

Characterisation of Connexin Expression and Electrophysiological Properties in Stable Clones of the HL-1 Myocyte Cell Line

et al. 2014

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The HL-1 atrial line contains cells blocked at various developmental stages. To obtain homogeneous sub-clones and correlate changes in gene expression with functional alterations, individual clones were obtained and characterised for parameters involved in conduction and excitation-contraction coupling. Northern blots for mRNAs coding for connexins 40, 43 and 45 and calcium handling proteins (sodium/calcium exchanger, L- and T-type calcium channels, ryanodine receptor 2 and sarco-endoplasmic reticulum calcium ATPase 2) were performed. Connexin expression was further characterised by western blots and immunofluorescence. Inward currents were characterised by voltage clamp and conduction velocities measured using microelectrode arrays. The HL-1 clones had similar sodium and calcium inward currents with the exception of clone 2 which had a significantly smaller calcium current density. All the clones displayed homogenous propagation of electrical activity across the monolayer correlating with the levels of connexin expression. Conduction velocities were also more sensitive to inhibition of junctional coupling by carbenoxolone (∼80%) compared to inhibition of the sodium current by lidocaine (∼20%). Electrical coupling by gap junctions was the major determinant of conduction velocities in HL-1 cell lines. In summary we have isolated homogenous and stable HL-1 clones that display characteristics distinct from the heterogeneous properties of the original cell line.

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Section: Discussionmentioning

confidence: 99%

Characterisation of Connexin Expression and Electrophysiological Properties in Stable Clones of the HL-1 Myocyte Cell Line

et al. 2014

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“…However, interest has grown recently in the possibility that these receptor subtypes are not redundant, but differentially regulate cardiac function. The distinct physiological actions of ␤ 1 AR and ␤ 2 AR may represent coupling to different signaling pathways (5)(6)(7)(8) and/or different spatial localization within the heart or within single cells (9,10).…”

mentioning

confidence: 99%

Receptor Number and Caveolar Co-localization Determine Receptor Coupling Efficiency to Adenylyl Cyclase

Ostrom

Gregorian

Drenan

et al. 2001

Journal of Biological Chemistry

232

213

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Recent evidence suggests that many signaling molecules localize in microdomains of the plasma membrane, particularly caveolae. In this study, overexpression of adenylyl cyclase was used as a functional probe of G protein-coupled receptor (GPCR) compartmentation. We found that three endogenous receptors in neonatal rat cardiomyocytes couple with different levels of efficiency to the activation of adenylyl cyclase type 6 (AC6), which localizes to caveolin-rich membrane fractions. Overexpression of AC6 enhanced the maximal cAMP response to ␤ 1 -adrenergic receptor (␤ 1 AR)-selective activation 3.7-fold, to ␤ 2 AR-selective activation only 1.6-fold and to prostaglandin E 2 (PGE 2 ) not at all. Therefore, the rank order of efficacy in coupling to AC6 is ␤ 1 AR > ␤ 2 AR > prostaglandin E 2 receptor (EP 2 R). ␤ 2 AR coupling efficiency was greater when we overexpressed the receptor or blocked its desensitization by expressing ␤ARKct, an inhibitor of G protein-coupled receptor kinase activation, but was not significantly greater when cells were treated with pertussis toxin. Assessment of receptor and AC expression indicated co-localization of AC5/6, ␤ 1 AR, and ␤ 2 AR, but not EP 2 R, in caveolin-rich membranes and caveolin-3 immunoprecipitates, likely explaining the observed activation of AC6 by ␤AR subtypes but lack thereof by PGE 2 . When cardiomyocytes were stimulated with a ␤AR agonist, ␤ 2 AR were no longer found in caveolin-3 immunoprecipitates; an effect that was blocked by expression of ␤ARKct. Thus, agonist-induced translocation of ␤ 2 AR out of caveolae causes a sequestration of receptor from effector and likely contributes to the lower efficacy of ␤ 2 AR coupling to AC6 as compared with ␤ 1 AR, which do not similarly translocate. Therefore, spatial co-localization is a key determinant of efficiency of coupling by particular extracellular signals to activation of GPCR-linked effectors.

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Depressed PKA Activity Contributes to Impaired SERCA Function and is Linked to the Pathogenesis of Glucose-induced Cardiomyopathy

Dutta

Carmody

Cala

et al. 2002

Journal of Molecular and Cellular Cardiology

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Coupling of β-Adrenergic Receptors to Cardiac L-Type Ca2+ Channels

Cited by 17 publications

References 17 publications

Characterisation of Connexin Expression and Electrophysiological Properties in Stable Clones of the HL-1 Myocyte Cell Line

Characterisation of Connexin Expression and Electrophysiological Properties in Stable Clones of the HL-1 Myocyte Cell Line

Receptor Number and Caveolar Co-localization Determine Receptor Coupling Efficiency to Adenylyl Cyclase

Depressed PKA Activity Contributes to Impaired SERCA Function and is Linked to the Pathogenesis of Glucose-induced Cardiomyopathy

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