What does this research mean for the field?

Agonist-free beta-adrenoceptors in intact guinea pig and human cardiac myocytes possess constitutive activity capable of stimulating L-type calcium currents, which can be inhibited by beta-adrenoceptor antagonists. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine whether agonist-free, empty beta-adrenoceptors directly stimulate L-type calcium currents in intact mammalian cardiac myocytes.

December 1, 1993CirculationOpen Access

Activation of calcium currents in cardiac myocytes by empty beta-adrenoceptors.

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Population

Cardiomyocytes isolated from ventricles of guinea pig and human hearts and from human right atrial appendage

Comparison

Beta-adrenoceptor antagonists without addition… vs Absence of beta-adrenoceptor antagonists

Design

Preclinical

Authors

TMTorsten MewesUniversity of Duisburg-Essen SDS Dutz URUrsula RavensElectrophysiology

Discussion

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Implication

No change to beta-blocker use indicated; leaves open whether agonist-free receptor effects translate to patients.

Key Points

To determine whether agonist-free, empty beta-adrenoceptors directly stimulate L-type calcium currents in intact mammalian cardiac myocytes.
Isolated ventricular and right atrial myocytes from guinea pig and human hearts were analyzed using single-electrode whole-cell patch-clamp electrophysiology.
L-type calcium currents (ICa) were recorded following exposure to subtype-selective and nonselective beta-blockers in the presence or absence of forskolin (0.5 μmol/L) or Sp-cAMPS (0.1 mmol/L).
In forskolin-sensitized myocytes, the beta 1-selective antagonist atenolol reversibly and stereoselectively inhibited ICa by up to 50% at 300 nmol/L (half-maximal inhibition at ~50 nmol/L), an effect shared by propranolol but not ICI 118,551.
In the absence of forskolin, atenolol (10 μmol/L) produced only an 18% reduction in ICa, and atenolol (1 μmol/L) failed to inhibit currents stimulated downstream by the protein kinase A activator Sp-cAMPS (0.1 mmol/L).

Structured PICO

Population

Cardiomyocytes isolated from ventricles of guinea pig and human hearts and from human right atrial appendage

Intervention

Beta-adrenoceptor antagonists (atenolol, propranolol, ICI 118,551) without addition of an agonist, in the absence and presence of forskolin or Sp-cAMPS

Comparator

Absence of beta-adrenoceptor antagonists

Outcome

Whole-cell L-type calcium currents (ICa)surrogate

This preclinical study demonstrates that agonist-free beta-adrenoceptors are functionally active and can stimulate L-type calcium currents in cardiac myocytes, an effect that can be blocked by receptor-specific antagonists.

Cite This Study

Mewes et al. (1993) studied this question.

synapsesocial.com/papers/6a76de233da069e66cbd6713 https://doi.org/10.1161/01.cir.88.6.2916

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Activation of calcium currents in cardiac myocytes by empty beta-adrenoceptors.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Activation of calcium currents in cardiac myocytes by empty beta-adrenoceptors.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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