Effects of etomidate on whole-cell and single L-type calcium channel currents in guineapig isolated ventricular myocytes. 1994

H Takahashi, and D A Terrar
Department of Anaesthetics, Radcliffe Infirmary, Oxford.

We have investigated the effects of etomidate 4.4 mumol litre-1, 1.0 mg litre-1 and 27.4 mumol litre-1, 6.25 mg litre-1 on whole-cell and single L-type calcium channel currents in myocytes from guineapig ventricles. For whole-cell recordings, the cells were voltage-clamped and step depolarizations were applied from holding potential of -40 mV to various potentials to elicit L-type calcium currents. Peak calcium currents were decreased significantly by both low and high concentrations of etomidate. Ethanol in the same concentration with the highest etomidate solution (1.1 mmol litre-1) had no significant effect on calcium currents. When single calcium channel activity was investigated, the high concentration of etomidate significantly decreased the open probability of the channel with little or no effect on channel conductance. Mean closed time was increased significantly, caused apparently by prolongation of the slower of two exponential components fitted to histograms of the closed times. The mean open time was virtually unaffected. The low concentration of etomidate did not significantly affect single channel kinetics. These results showed that etomidate decreased L-type calcium current by altering the kinetics of the channel to favour the closed state without any significant change in conductance. However, compared with other anaesthetics which were investigated previously in our laboratory, the overall effect on calcium current appeared to be small.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005045 Etomidate Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic. Ethomidate,Hypnomidate,R-26490,Radenarkon,R 26490,R26490
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015220 Calcium Channels Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. Ion Channels, Calcium,Receptors, Calcium Channel Blocker,Voltage-Dependent Calcium Channel,Calcium Channel,Calcium Channel Antagonist Receptor,Calcium Channel Antagonist Receptors,Calcium Channel Blocker Receptor,Calcium Channel Blocker Receptors,Ion Channel, Calcium,Receptors, Calcium Channel Antagonist,VDCC,Voltage-Dependent Calcium Channels,Calcium Channel, Voltage-Dependent,Calcium Channels, Voltage-Dependent,Calcium Ion Channel,Calcium Ion Channels,Channel, Voltage-Dependent Calcium,Channels, Voltage-Dependent Calcium,Voltage Dependent Calcium Channel,Voltage Dependent Calcium Channels

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