Related Experiment Video

Updated: Aug 5, 2026

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method
10:53

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method

Published on: February 26, 2018

Effects of kappa-opioid receptor activation on myocardium

W G Pyle1, J W Lester, P A Hofmann

  • 1Department of Physiology, University of Tennessee, Memphis, Tennessee 38163, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|July 17, 2001
PubMed

Insights

Kappa-opioid receptor activation increases heart twitch amplitude and Ca2+ sensitivity via protein kinase C (PKC). This pathway also modulates myocardial energy by reducing ATP consumption, impacting cardiac function.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Cardiac Muscle Mechanics

Background:

  • Kappa-opioid receptor (KOR) stimulation affects cardiac contractility and actomyosin ATPase activity through unknown mechanisms.
  • The role of myofilament Ca2+ sensitivity and protein kinase C (PKC) in KOR-mediated cardiac effects requires elucidation.

Purpose of the Study:

  • To investigate if KOR stimulation alters myofilament Ca2+ sensitivity, contributing to increased twitch amplitude.
  • To determine if KOR activation affects actomyosin ATPase activity and tension Ca2+ sensitivity consistent with PKC action.
  • To explore the impact of KOR-PKC pathway on myocardial energy status.

Main Methods:

  • Isolated rat hearts and myofibrils were treated with KOR agonist (U50,488H), adrenergic agonists, or PKC activator (PMA).
  • Measurements included Ca2+-dependent actomyosin Mg2+-ATPase activity, ventricular ATP levels, and Ca2+ sensitivity of isometric tension in isolated myocytes.
  • PKC inhibitors were used to assess the involvement of this kinase pathway.

Main Results:

  • KOR stimulation (U50,488H), alpha-adrenergic stimulation, and PMA decreased actomyosin Mg2+-ATPase activity, while beta-adrenergic stimulation increased it.
  • PKC activation (endogenous or exogenous PKC-epsilon) reduced actomyosin Mg2+-ATPase activity.
  • KOR activation and PMA increased myocyte Ca2+ sensitivity of tension, an effect retained at reduced pH.
  • PKC inhibition abolished KOR effects on ATPase activity and myocardial ATP levels.
  • Ventricular ATP levels were higher in KOR-stimulated hearts.

Conclusions:

  • Kappa-opioid receptor activation likely enhances cardiac contractility through a PKC-mediated increase in myofilament Ca2+ sensitivity.
  • The KOR-PKC pathway modulates myocardial energy status by decreasing actomyosin ATP consumption.
  • These findings elucidate a novel signaling pathway influencing cardiac function and energy metabolism.

More Related Videos

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury07:23

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury

Published on: March 7, 2022

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique08:11

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique

Published on: November 11, 2022

Related Concept Videos

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,...
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive 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,...
Pathophysiology of Cardiac Performance01:29

Pathophysiology of Cardiac Performance

Typical heart performance is influenced by heart rate, rhythm, myocardial contraction, and metabolism or blood flow. The cardiac muscle exhibits distinct electrophysiological features, including pacemaker activity and calcium channel control, which play a vital role in the heart's response to various drugs. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, regulates heart rate. Sympathetic activation increases heart rate, while parasympathetic activation...
Heart Failure Drugs: Inotropic Agents01:26

Heart 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...
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
Analgesia and Pain Management01:25

Analgesia and Pain Management

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...