Related Experiment Video

Updated: May 17, 2026

Exploring Arterial Smooth Muscle Kv7 Potassium Channel Function using Patch Clamp Electrophysiology and Pressure Myography
11:02

Exploring Arterial Smooth Muscle Kv7 Potassium Channel Function using Patch Clamp Electrophysiology and Pressure Myography

Published on: September 14, 2012

K(ATP) channels mediate the antihypertrophic effects afforded by κ-opioid receptor stimulation in neonatal rat

Lei Zhang1, Hongxin Wang, Meili Lu

  • 1Key Laboratory of Molecular Biology and Drug Research, Liaoning Medical College, Jinzhou 121001, P.R. China ;

Experimental and Therapeutic Medicine
|November 10, 2012
PubMed

Insights

κ-opioid receptor (OR) agonists prevent cardiac hypertrophy by activating K(ATP) channels, particularly mitochondrial K(ATP) (mitoK(ATP)). This pathway involves protein kinase C (PKC) and reduces intracellular calcium transients.

Area of Science:

  • Cardiology
  • Pharmacology
  • Molecular Biology

Background:

  • Cardiac hypertrophy is a significant risk factor for heart failure.
  • κ-opioid receptors (ORs) and K(ATP) channels are implicated in regulating cardiac myocyte function.
  • Previous studies suggest potential antihypertrophic roles for both OR agonists and K(ATP) channel activation.

Purpose of the Study:

  • To investigate the antihypertrophic effects of κ-opioid receptor (OR) agonists in neonatal rat ventricular myocytes.
  • To determine the role of K(ATP) channels, including mitochondrial (mitoK(ATP)) and sarcolemmal (sarcK(ATP)) subtypes, in mediating these OR effects.
  • To elucidate the signaling pathway connecting ORs, K(ATP) channels, and intracellular calcium ([Ca(2+)](i)) transients.

Main Methods:

  • Primary cultures of neonatal rat ventricular myocytes were exposed to phenylephrine to induce hypertrophy.
  • The effects of the selective κ-OR agonist U50,488H were assessed on hypertrophy markers (protein content, cell size, [(3)H]leucine incorporation) and [Ca(2+)](i) transients.
  • Pharmacological inhibitors of κ-OR (nor-binaltorphimine), protein kinase C (chelerythrine), and K(ATP) channels (glibenclamide, 5-hydroxydecanoic acid) were used.
  • Expression of Kir6.2 subunits of the K(ATP) channel was analyzed.

Main Results:

  • Phenylephrine induced significant cardiac hypertrophy and elevated [Ca(2+)](i) transients.
  • U50,488H, a κ-OR agonist, prevented phenylephrine-induced hypertrophy and normalized [Ca(2+)](i) transients, an effect blocked by nor-binaltorphimine.
  • The antihypertrophic effect of U50,488H was reversed by K(ATP) channel inhibitors (glibenclamide and 5-hydroxydecanoic acid), with no significant difference between nonselective and mitoK(ATP) selective inhibitors.
  • U50,488H increased Kir6.2 subunit expression, which was abrogated by inhibitors.
  • The protein kinase C inhibitor chelerythrine also reversed the antihypertrophic effect of U50,488H.

Conclusions:

  • κ-opioid receptor stimulation exerts antihypertrophic effects on cardiac myocytes.
  • These effects are mediated by K(ATP) channels, with a significant contribution from mitochondrial K(ATP) (mitoK(ATP)).
  • The protein kinase C (PKC) signaling pathway is involved in the cross-talk between κ-ORs and K(ATP) channels, ultimately impacting intracellular calcium levels.

More Related Videos

Measuring Cation Transport by Na,K- and H,K-ATPase in Xenopus Oocytes by Atomic Absorption Spectrophotometry: An Alternative to Radioisotope Assays12:48

Measuring Cation Transport by Na,K- and H,K-ATPase in Xenopus Oocytes by Atomic Absorption Spectrophotometry: An Alternative to Radioisotope Assays

Published on: February 19, 2013

Related Concept Videos

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,...
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,...
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...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
ATP Driven Pumps III: V-type Pumps01:30

ATP Driven Pumps III: V-type Pumps

V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.