Related Experiment Video
Updated: Aug 8, 2026
09:36
Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device
Published on: September 24, 2020
Halothane depresses D600 binding to bovine heart sarcolemma
P J Hoehner1, M C Quigg, T J Blanck
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Anesthesiology
|December 1, 1991
Summary
Volatile anesthetics like halothane reduce functional calcium channels in heart cells, decreasing calcium entry and potentially causing negative inotropic effects. This effect is dose-dependent and reversible.
Area of Science:
- Cardiovascular Pharmacology
- Anesthesiology
- Molecular Cardiology
Background:
- Volatile anesthetics can negatively impact heart contractility by altering calcium (Ca2+) homeostasis.
- The precise dose-dependent mechanism underlying this negative inotropic effect remains unclear.
- Calcium channels are crucial for myocardial function and Ca2+ regulation.
Purpose of the Study:
- To investigate the effect of halothane on the binding characteristics of voltage-dependent calcium channels (VDCCs) in bovine heart sarcolemma.
- To determine if halothane alters the interaction of a Ca2+-channel antagonist with VDCCs.
Main Methods:
- Purified bovine heart sarcolemmal vesicles were prepared using differential centrifugation and filtration.
- 3H-D600 (a Ca2+-channel antagonist) equilibrium binding assays were conducted.
- Assays were performed in the presence of varying halothane concentrations (0.7%, 1.3%, 2.5%) and unlabeled D600 to assess specific and nonspecific binding.
Main Results:
- Halothane significantly reduced 3H-D600 specific binding to VDCCs in a dose-dependent and reversible manner.
- A halothane concentration of 1.3% caused a 40% decrease in the maximum binding capacity (Bmax) of VDCCs.
- The dissociation constant (Kd) for 3H-D600 binding was unaffected by halothane exposure.
Conclusions:
- Volatile anesthetics, such as halothane, may induce negative inotropy by reducing the number of functional VDCCs in the heart.
- This reduction in functional VDCCs leads to decreased Ca2+ influx into myocardial cells.
- The findings support a mechanism where impaired Ca2+ entry contributes to the cardiac side effects of volatile anesthetics.
Related Concept Videos
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
β-receptor blockers significantly impact the cardiovascular system by counteracting catecholamine-induced sympathetic responses. These medications decrease heart rate, contractility, and cardiac output, potentially leading to cardiac depression, life-threatening bradycardia, and death. Therapeutically, β-blockers function as mild antihypertensives and are utilized in treating angina pectoris and cardiac arrhythmias. However, nonselective β-blockers inhibit β2-receptors in bronchial smooth...
01:27Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacological Actions
Nondepolarizing neuromuscular blockers prevent the membrane depolarization of muscle cells and inhibit muscle contraction. These are usually administered with anesthetics to achieve complete muscle relaxation. Upon administration, these drugs first block the small, rapidly contracting muscles of the face and hands, followed by the larger muscles of the trunk and the intercostal muscles. The diaphragm is the last muscle to be affected.
Although all competitive neuromuscular blockers are designed...
Although all competitive neuromuscular blockers are designed...
01:28Depolarizing Blockers: Mechanism of Action
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because succinylcholine...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because succinylcholine...
01:19Depolarizing Blockers: Pharmocokinetics
Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which...
01:21Skeletal Muscle Relaxants: Adverse Effects
Skeletal muscle relaxants are widely used for muscle paralysis and relieving pain following any muscle injury or stiffness. However, depending on the drug type, they can have adverse effects that range from mild to severe. Usually, nondepolarizing neuromuscular blockers have minimal side effects. For example, drugs like d-tubocurarine, cisatracurium, and rocuronium cause hypotension, whereas drugs like baclofen, when stopped abruptly, can lead to the recurrence of spastic conditions.
Unlike...
Unlike...
01:22Heart Failure Drugs: β-Blockers
β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation, vasodilation, and...