Related Experiment Video
Updated: Jul 17, 2026
07:42
Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates
Published on: October 18, 2018
Hypericin activates L-type Ca2+ channels in cardiac myocytes
Martin-Pierre Sauviat1, Anthony Colas, Marie-Jeanne Chauveau
1Laboratoire d'Optique et Biosciences, U696 INSERM, UMR7645 CNRS, X/ENSTA, Ecole Polytechnique, Route de Saclay, 91128 Palaiseau Cedex, France. martin-pierre.sauviat@polytechnique.edu
Journal of Natural Products
|February 13, 2007
Summary
Hypericin prolongs cardiac action potential duration by increasing L-type Ca2+ channel conductance. This effect is mediated by inhibiting soluble guanylate cyclase (sGC) and reducing cellular cGMP levels in frog atrial myocytes.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Molecular Cardiology
Background:
- Hypericin's effects on cardiac electrophysiology remain incompletely understood.
- Investigating hypericin's impact on action potential and L-type Ca2+ channels is crucial for understanding its cardiac actions.
Purpose of the Study:
- To elucidate the effects and mechanism of action of hypericin on frog atrial heart muscle.
- To determine hypericin's influence on the action potential (AP) and L-type Ca2+ channels.
Main Methods:
- Intracellular microelectrode and patch-clamp techniques were employed.
- Experiments were conducted on frog atrial heart muscle in modified Ringer solutions.
- Specific blockers for adrenoceptors, PKC, and soluble guanylate cyclase (sGC) were utilized.
Main Results:
- Hypericin (4 microM) prolonged action potential duration (APD) in Sr2+-containing solution.
- Hypericin dose-dependently increased L-type Ca2+ channel current magnitude without altering kinetics.
- Inhibition of sGC by 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one mimicked hypericin's APD lengthening effect.
- Hypericin decreased cellular cGMP levels by 69% through sGC inhibition.
Conclusions:
- Hypericin increases L-type Ca2+ channel conductance, leading to APD prolongation.
- The mechanism involves the inhibition of soluble guanylate cyclase (sGC) and subsequent reduction in cellular cGMP.
- Hypericin's action on cardiac L-type Ca2+ channels is independent of adrenoceptor and PKC signaling pathways.
Related Concept Videos
01:21G-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,...
Sensory organs,...
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
01:26Heart Failure Drugs: Inotropic Agents
Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
01:20Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
01:27Feedback 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...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:24Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers
Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...