Volatile Anesthetics Reduce Calcium Current in Parasympathetic Neurons from Bullfrog Hearts

Abstract
Although the autonomic nervous system regulates cardiac function, the cellular mechanism(s) of general anesthetics on the activities of parasympathetic neurons have not been directly assessed. We therefore studied the volatile anesthetic actions on the Ca2+ current of parasympathetic neurons isolated from bullfrog hearts. Neurons were enzymatically isolated from the interatrial septum of bullfrog heart and maintained in a short-term tissue culture. The Ca2+ current was recorded with a whole-cell voltage-clamp method under a Na+, K+ -free condition. Isoflurane (2.5 vol%) and sevoflurane (5.0 vol%) reduced the peak amplitude of the Ca2+ current (to 79% and 72% of control, respectively) without changing the reversal potential. The curve-fit analysis of the inactivation kinetics revealed that isoflurane and sevoflurane accelerated the inactivation of the current and that isoflurane shifted the midpoint of the steady-state inactivation curve of the Ca2+ current toward negative by 13.6 mV. The results indicate that volatile anesthetics reduce the Ca2+ current of parasympathetic neurons and modify the inactivation kinetics. The anesthetic reduction of the Ca2+ current of parasympathetic neurons can induce a decrease of acetylcholine release from the post-ganglionic endings. These findings, in part, account for the anesthetic attenuation of the vagal efferent activities observed in humans and experimental animals.