Effects of Halothane and Isoflurane on Calcium and Potassium Channel Currents in Canine Coronary Arterial Cells

Buljubasic, Nediljka; Rusch, Nancy J.; Marijic, Jure; Kampine, John P.; Bošnjak, Željko J.

doi:10.1097/00000542-199206000-00020

Cited by 80 publications

(40 citation statements)

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“…While BaCl 2 is a relatively potent I K1 blocker, barium alters calcium-mediated inactivation of the L-type calcium channel (6). However, this study used doses of BaCl 2 orders of magnitude smaller (mol/l) than those reported to significantly alter L-type calcium channel kinetics (mmol/l) (3). Like all nonspecific blockers, the potential for nonspecific electrophysiological effects may complicate interpretation.…”

Section: Discussionmentioning

confidence: 90%

Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig

Poelzing¹,

Veeraraghavan²

2007

American Journal of Physiology-Heart and Circulatory Physiology

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Poelzing S, Veeraraghavan R. Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig. Am J Physiol Heart Circ Physiol 292: H3043-H3051, 2007. First published February 16, 2007; doi:10.1152/ajpheart.01312.2006.-It was previously demonstrated that transmural electrophysiological heterogeneities can inscribe the ECG T wave. However, the bifurcated T wave caused by loss of inward rectifier potassium current (IK1) function is not fully explained by transmural heterogeneities. Since right ventricular (RV) guinea pig myocytes have significantly lower IK1 than left ventricular (LV) myocytes, we hypothesized that the complex ECG can be inscribed by heterogeneous chamber-specific responses to hypokalemia and partial IK1 blockade. Ratiometric optical action potentials were recorded from the epicardial surface of the RV and LV. BaCl2 (10 mol/l) was perfused to partially block IK1 in isolated guinea pig whole heart preparations. BaCl2 or hypokalemia alone significantly increased RV basal (RVB) action potential duration (APD) by ϳ30% above control compared with LV apical (LVA) APD (14%, P Ͻ 0.05). In the presence of BaCl2, 2 mmol/l extracellular potassium (hypokalemia) further increased RVB APD to a greater extent (31%) than LVA APD (19%, P Ͻ 0.05) compared with BaCl2 perfusion alone. Maximal dispersion between RVB and LVA APD increased by 105% (P Ͻ 0.05), and the QT interval prolonged by 55% (P Ͻ 0.05) during hypokalemia and BaCl2. Hypokalemia and BaCl2 produced an ECG with a double repolarization wave. The first wave (QT1) corresponded to selective depression of apical LV plateau potentials, while the second wave (QT2) corresponded to the latest repolarizing RV B myocytes. These data suggest that final repolarization is more sensitive to extracellular potassium changes in regions with reduced I K1, particularly when I K1 availability is reduced. Furthermore, underlying I K1 heterogeneities can potentially contribute to the complex ECG during I K1 loss of function and hypokalemia. electrophysiology; waves; electrocardiography; interventricular heterogeneities; inward rectifier potassium current IT IS WELL ESTABLISHED THAT electrophysiological heterogeneities inscribe the distinct ECG morphology. The T wave, representing final repolarization, has been linked to dispersion of repolarization across the ventricular wall (40). However, the preferential appearance of bifurcated T waves in leads II and V 3 during hypokalemia (39) suggests that the predominant heterogeneity during hypokalemia may be regional rather than transmural.Interestingly, hypokalemia has dichotomous effects on repolarizing potassium currents. For example, the inward rectifier potassium current (I K1 ) has a paradoxical relationship withwhere I K1 peak current density is reduced during hypokalemia (28). I K1 plays an important role in ventricular action potentials by modulating resting membrane potential and final repolarization. In humans, I K1 reduction, as occurs in ...

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Section: Discussionmentioning

confidence: 90%

Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig

Poelzing¹,

Veeraraghavan²

2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…Such methods are already available, for example, multiphoton microscopy of brain arterioles 77,78 and localized uncaging of Ca 2 þ or IP 3 in a single or few cells. [79][80][81] As gap junctions, voltage-gated Ca 2 þ channels and endothelial-dependent responses are known to be sensitive to anesthetic concentrations of propofol, thiopental, halothane, isoflurane, sevoflurane, and other general anesthetic agents [82][83][84][85][86][87] it is of paramount importance to validate the method of anesthesia carefully in such in vivo studies.…”

Section: Perspectives For Studying Cerebral Vascular Conducted Responsesmentioning

confidence: 99%

The Vascular Conducted Response in Cerebral Blood Flow Regulation

Jensen¹,

Holstein‐Rathlou

2013

J Cereb Blood Flow Metab

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Despite recent advances in our understanding of the molecular and cellular mechanisms behind vascular conducted responses (VCRs) in systemic arterioles, we still know very little about their potential physiological and pathophysiological role in brain penetrating arterioles controlling blood flow to the deeper areas of the brain. The scope of the present review is to present an overview of the conceptual, mechanistic, and physiological role of VCRs in resistance vessels, and to discuss in detail the recent advances in our knowledge of VCRs in brain arterioles controlling cerebral blood flow. We provide a schematic view of the ion channels and intercellular communication pathways necessary for conduction of an electrical and mechanical response in the arteriolar wall, and discuss the local signaling mechanisms and cellular pathway involved in the responses to different local stimuli and in different vascular beds. Physiological modulation of VCRs, which is a rather new finding in this field, is discussed in the light of changes in plasma membrane ion channel conductance as a function of health status or disease. Finally, we discuss the possible role of VCRs in cerebrovascular function and disease as well as suggest future directions for studying VCRs in the cerebral circulation.

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“…Thiopental blocks I Ks and inward rectifier K ϩ current (I K1 ) (11,16,27,38). Additionally, all three agents block the L-type Ca 2ϩ current (I Ca,L ) (9,10,38), which shortens the action potential duration (APD) and hence reduces their QT prolonging effect. Although the sedative midazolam inhibits I K1 in vitro (9), changes in QT duration have not been detected in healthy humans (25,26).…”

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confidence: 99%

Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization

Odening

Hyder

Chaves

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization. Am J Physiol Heart Circ Physiol 295: H2264 -H2272, 2008. First published October 3, 2008 doi:10.1152/ajpheart.00680.2008.-Anesthetic agents prolong cardiac repolarization by blocking ion currents. However, the clinical relevance of this blockade in subjects with reduced repolarization reserve is unknown. We have generated transgenic long QT syndromes type 1 (LQT1) and type 2 (LQT2) rabbits that lack slow delayed rectifier K ϩ currents (IKs) or rapidly activating K ϩ currents (IKr) and used them as a model system to detect the channel-blocking properties of anesthetic agents. Therefore, LQT1, LQT2, and littermate control (LMC) rabbits were administered isoflurane, thiopental, midazolam, propofol, or ketamine, and surface ECGs were analyzed. Genotype-specific heart rate correction formulas were used to determine the expected QT interval at a given heart rate. The QT index (QTi) was calculated as percentage of the observed QT/expected QT. Isoflurane, a drug that blocks IKs, prolonged the QTi only in LQT2 and LMC but not in LQT1 rabbits. Midazolam, which blocks inward rectifier K ϩ current (IK1), prolonged the QTi in both LQT1 and LQT2 but not in LMC. Thiopental, which blocks both IKs and IK1, increased the QTi in LQT2 and LMC more than in LQT1. By contrast, ketamine, which does not block IKr, IKs, or IK1, did not alter the QTi in any group. Finally, anesthesia with isoflurane or propofol resulted in lethal polymorphic ventricular tachycardia (pVT) in three out of nine LQT2 rabbits. Transgenic LQT1 and LQT2 rabbits could serve as an in vivo model in which to examine the pharmacogenomics of drug-induced QT prolongation of anesthetic agents and their proarrhythmic potential. Transgenic LQT2 rabbits developed pVT under isoflurane and propofol, underlining the proarrhythmic risk of IKs blockers in subjects with reduced I Kr . repolarization reserve; long QT syndrome types 1 and 2; sudden cardiac death; ventricular fibrillation COMMONLY USED ANESTHETIC AGENTS influence cardiac repolarization, with effects on surface ECG such as changes in QT interval duration and T-wave morphology (23,26,37,41). Drug-induced QT prolongation is known to precede potentially lethal arrhythmias such as polymorphic ventricular tachycardia (pVT) (reviewed in Refs. 3 and 15). The risk for anesthesiainduced malignant pVT is particularly pronounced in individuals with congenital long QT (LQT) syndromes (LQTS) (2,14,17,18,31,35,40) (12) are responsible for the LQT1 and LQT2 phenotypes, respectively. Furthermore, subtle mutations in LQT-related genes can predispose healthy individuals to drug-induced QT prolongation and ventricular arrhythmia (20,22,29,51). Therefore, anesthetic agents might have more serious implications for apparently healthy individuals in the general population.In vitro patch-clamp experiments have revealed that several anesthetic drugs block cardiac repolarizing ion currents; isoflurane (47) and pro...

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Effects of Halothane and Isoflurane on Calcium and Potassium Channel Currents in Canine Coronary Arterial Cells

Cited by 80 publications

References 0 publications

Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig

Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig

The Vascular Conducted Response in Cerebral Blood Flow Regulation

Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization

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