Faculty Collaboration Database

Differential modulation of the cardiac L- and T-type calcium channel currents by isoflurane. Anesthesiology 2001 Aug;95(2):515-24

Date

08/17/2001

Pubmed ID

11506128

DOI

10.1097/00000542-200108000-00038

Scopus ID

2-s2.0-0034895175 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

BACKGROUND: Volatile anesthetics exert their negative chronotropic and inotropic effects, in part by depressing the L- and T-type calcium channels. This study examines and compares the dose-dependent effects of isoflurane on atrial L- and T-type calcium currents (I(Ca,L) and I(Ca,T)) and ventricular I(Ca,L).

METHODS: Whole cell I(Ca) was recorded from enzymatically isolated guinea pig cardiomyocytes. Current-voltage relations for atrial and ventricular I(Ca,L) was obtained from holding potentials of -90 and -50 mV to test a potential of +60 mV in 10-mV increments. Atrial I(Ca,T) was determined by subtraction of currents obtained from holding potentials of -50 and -90 mV. Steady state inactivation was determined using standard two-pulse protocols, and data were fitted with the Boltzmann equation.

RESULTS: Isoflurane depressed I(Ca) in a dose-dependent manner, with Kd values of 0.23+/-0.03, 0.34+/-0.03, and 0.71+/-0.02 mM of anesthetic for atrial I(Ca,T) and I(Ca,L) and ventricular (ICa,L), respectively, and caused a significant (P < 0.05) hyperpolarizing shift in steady state inactivation. At 1.2 and 1.6 mm, isoflurane caused a significant (P < 0.05) depolarizing shift in the steady state activation in ventricular I(Ca,L) but not in atrial I(Ca,L) or I(Ca,T). In addition to the depression of I(Ca,L), isoflurane also induced a hyperpolarizing shift in the reversal potential of I(Ca) for both atrial and ventricular L-type calcium channels.

CONCLUSION: The results show that atrial I(Ca,T) is more sensitive to isoflurane than atrial I(Ca,L), and ventricular I(Ca,L) was the least responsive to the anesthetic. These differential sensitivities of the calcium channels in the atrial and ventricular chambers might reflect phenotypic differences in the calcium channels or differences in modulation by the anesthetic.

Author List

Camara AK, Begic Z, Kwok WM, Bosnjak ZJ

Authors

Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of Wisconsin
Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
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

Algorithms
Anesthetics, Inhalation
Animals
Calcium Channels, L-Type
Calcium Channels, T-Type
Cell Separation
Guinea Pigs
Heart
Heart Atria
Heart Ventricles
In Vitro Techniques
Indicators and Reagents
Isoflurane
Myocardium
Patch-Clamp Techniques