The Role of L-Type Voltage-Dependent Calcium Channels in Anesthetic Depression of Contractility

Abstract

In this chapter data are presented to show that not only halothane but also enflurane and isoflurane decrease the density of binding sites for the calcium antagonist [ 3 H]isradipine in adult and newborn rabbit myocardial membranes. The chapter provides an observation that halothane can interfere with the binding of calcium channel antagonist (CCA) to cardiac L-type voltage-dependent Ca 2+ channel (VDCC). It has been convincingly demonstrated that the other volatile anesthetics, enflurane and isoflurane, are both able to interfere with the binding of a radiolabeled dihydropyridine, [ 3 H]isradipine, to both cardiac and skeletal muscle membranes. This phenomenon is relevant to anesthetic depression of contractility in an intact organ. Halothane can actually protect VDCC from blockade by isradipine. However, the sites have been protected by halothane appear to have a markedly lower affinity for [ 3 H]isradipine than the sites that has been untouched by halothane. The decreased affinity that has been observed in the VDCC, “protected” by halothane suggests that halothane is either modifying the VDCC or selecting an independent group of VDCC. Isradipine is known to bind to inactive channels with high affinity, and it is possible that halothane “protects” channels that are in the “unavailable” state or that have been modified by phosphorylation or other mechanisms resulting in a change of the K d for isradipine. This is a distinctly different result from previous in vitro data and from the K d values obtained from control hearts and hearts perfused with isradipine alone.