Related Experiment Video

Updated: Aug 9, 2026

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
11:00

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

Modulation of cardiac sarcoplasmic reticulum calcium release by aenosine: a protein kinase C- dependent pathway

Sandra Ghelardoni1, Sabina Frascarelli, Vittoria Carnicelli

  • 1Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Pisa, Italy.

Molecular and Cellular Biochemistry
|April 4, 2006
PubMed

Insights

Stimulating the A(3) adenosine receptor in rat hearts reduces calcium release via protein kinase C activation. This effect does not involve phospholipase C or direct ryanodine receptor modification.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Adenosine Receptor Signaling

Background:

  • A(3) adenosine receptor stimulation was previously shown to reduce sarcoplasmic reticulum Ca(2+) release in rat hearts.
  • The specific intracellular signaling pathway mediating this effect remained to be elucidated.

Purpose of the Study:

  • To investigate the transduction pathway responsible for A(3) adenosine receptor-mediated reduction of sarcoplasmic reticulum Ca(2+) release.
  • To determine the role of phospholipase C and protein kinase C in this signaling cascade.

Main Methods:

  • Isolated rat hearts were perfused with an A(3) adenosine agonist (IB-MECA), a phospholipase C inhibitor (U-73122), or a protein kinase C inhibitor (chelerythrine).
  • [(3)H]-ryanodine binding was measured to assess sarcoplasmic reticulum Ca(2+) release.
  • Gene expression (RT-PCR) and protein phosphorylation (Western blot) of the ryanodine receptor were analyzed.

Main Results:

  • A(3) adenosine receptor agonist (IB-MECA) significantly decreased ryanodine binding.
  • This decrease was abolished by chelerythrine (protein kinase C inhibitor) but not by U-73122 (phospholipase C inhibitor).
  • IB-MECA did not affect ryanodine receptor gene expression or phosphorylation at serine 2809.

Conclusions:

  • A(3) adenosine receptor modulation of SR Ca(2+) release is dependent on protein kinase C activation.
  • Protein kinase C activation in this context is not mediated by phospholipase C.
  • Changes in ryanodine receptor gene expression or direct phosphorylation are not involved in this inhibitory effect.

More Related Videos

Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+12:30

Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+

Published on: May 19, 2017

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...