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October 26, 2010British Journal of PharmacologyOpen Access

Effects of β‐adrenoceptor stimulation on delayed rectifier K+ currents in canine ventricular cardiomyocytes

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Key result

Stimulation of β1-adrenoceptors by isoprenaline significantly increased the rapid delayed rectifier K+ current (I(Kr)) by 30-50% via the activation of PKA in canine ventricular cells.

Why the study?

Does β₁-adrenoceptor stimulation increase rapid and slow delayed rectifier K⁺ currents via PKA activation in canine ventricular cardiomyocytes?

Population

Canine ventricular cardiomyocytes

Comparison

Isoprenaline, forskolin, or intracellular… vs Baseline conditions, selective β₁-adrenoceptor…

Design

Preclinical

Authors

GHGábor HarmatiBalaton Limnological InstituteTBTamás BányászUniversity of DebrecenLBLászló BárándiUniversity of Debrecen

Discussion

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Implication

May influence canine repolarization reserve; leaves open human arrhythmia relevance.

Structured PICO

Does β₁-adrenoceptor stimulation increase rapid and slow delayed rectifier K⁺ currents via PKA activation in canine ventricular cardiomyocytes?

P
Population
Canine ventricular cardiomyocytes
I
Intervention
Isoprenaline (ISO), forskolin, or intracellular application of PKA activator cAMP analogues (cAMP, 8-Br-cAMP, 6-Bnz-cAMP)
C
Comparator
Baseline conditions, selective β₁-adrenoceptor antagonists (metoprolol and CGP-20712A), PKA inhibitor (Rp-8-Br-cAMP), or EPAC activator (8-pCPT-2'-O-Me-cAMP)
O
Outcome
Effect on rapid delayed rectifier K⁺ current (I(Kr)) and slow delayed rectifier K⁺ current (I(Ks)) measured via whole cell patch clamp techniquesurrogate

Stimulation of β₁-adrenoceptors increases both rapid and slow delayed rectifier K⁺ currents via the activation of PKA in canine ventricular cells.

Cite This Study

Harmati et al. (2010) studied this question. Isoprenaline (ISO) and PKA pathway activators vs. Baseline / PKA inhibitors was evaluated on Rapid delayed rectifier K(+) current (I(Kr)) and slow delayed rectifier K(+) current (I(Ks)). Stimulation of β1-adrenoceptors by isoprenaline significantly increased the rapid delayed rectifier K+ current (I(Kr)) by 30-50% via the activation of PKA in canine ventricular cells.

synapsesocial.com/papers/6a208886ee274fb2963e8947https://doi.org/10.1111/j.1476-5381.2010.01092.x
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Protein kinase C enhances the rapidly activating delayed rectifier potassium current, <i>I</i><sub>Kr</sub>, through a reduction in C‐type inactivation in guinea‐pig ventricular myocytes2000 · 114 citations
  2. 2Two Components of Delayed Rectifier Current in Canine Atrium and Ventricle1996 · 138 citations
  3. 3cAMP compartmentation is responsible for a local activation of cardiac Ca2+ channels by beta-adrenergic agonists.1996 · 375 citations
  4. 4Evidence for Two Components of Delayed Rectifier K<sup>+</sup>Current in Human Ventricular Myocytes1996 · 469 citations
  5. 5Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein2003 · 69 citations