Faculty Collaboration Database

Modulation of cardiac sodium current by alpha1-stimulation and volatile anesthetics. Anesthesiology 1997 Dec;87(6):1507-16

Date

01/07/1998

Pubmed ID

9416736

DOI

10.1097/00000542-199712000-00030

Scopus ID

2-s2.0-0031442019 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

BACKGROUND: Alpha1-adrenoceptor stimulation is known to produce electrophysiologic changes in cardiac tissues, which may involve modulations of the fast inward Na+ current (I(Na)). A direct prodysrhythmic alpha1-mediated interaction between catecholamines and halothane has been demonstrated, supporting the hypothesis that generation of halothane-epinephrine dysrhythmias may involve slowed conduction, leading to reentry. In this study, we examined the effects of a selective alpha1-adrenergic receptor agonist, methoxamine, on cardiac I(Na) in the absence and presence of equianesthetic concentrations of halothane and isoflurane in single ventricular myocytes from adult guinea pig hearts.

METHODS: I(Na) was recorded using the standard whole-cell configuration of the patch-clamp technique. Voltage clamp protocols initiated from two different holding potentials (V(H)) were applied to examine state-dependent effects of methoxamine in the presence of anesthetics. Steady state activation and inactivation and recovery from inactivation were characterized using standard protocols.

RESULTS: Methoxamine decreased I(Na) in a concentration- and voltage-dependent manner, being more potent at the depolarized V(H). Halothane and isoflurane interacted synergistically with methoxamine to suppress I(Na) near the physiologic cardiac resting potential of -80 mV. The effect of methoxamine with anesthetics appeared to be additive when using a V(H) of -110 mV, a potential where no Na+ channels are in the inactivated state. Methoxamine in the absence and presence of anesthetics significantly shifted the half maximal inactivation voltage in the hyperpolarizing direction but had no effect on steady-state activation.

CONCLUSION: The present results show that methoxamine (alpha1-adrenergic stimulation) decreases cardiac Na+ current in a concentration- and voltage-dependent manner. Further, a form of synergistic interaction between methoxamine and inhalational anesthetics, halothane and isoflurane, was observed. This interaction appears to depend on the fraction of Na+ channels in the inactivated state. (Key words: Anesthetics, volatile: halothane; isoflurane; methoxamine. Patch clamp: whole-cell configuration; sodium current; ventricular guinea pig myocytes.)

Author List

Weigt HU, Kwok WM, Rehmert GC, Turner LA, Bosnjak ZJ

Author

Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic alpha-Agonists
Anesthetics, Inhalation
Animals
Drug Interactions
Guinea Pigs
Halothane
Heart
Methoxamine
Myocardium
Patch-Clamp Techniques
Sodium Channels