Modulation of hyperpolarization-activated cation current I by volatile anesthetic sevoflurane in the mouse striatum during postnatal development.

Volatile anesthetics have been reported to inhibit hyperpolarization-activated cyclic-nucleotide gated channels underlying the hyperpolarization-activated cation current (I) that contributes to generation of synchronized oscillatory neural rhythms. Meanwhile, the developmental change of I has been speculated to play a pivotal role during maturation. In this study, we examined the effect of the volatile anesthetic sevoflurane, which is widely used in pediatric surgery, on I and on functional I activation kinetics of cholinergic interneurons in developing striatum. Our analyses showed that the changes in I of cholinergic interneurons occurred in conjunction with maturation. Sevoflurane application (1-4%) caused significant inhibition of I in a dose-dependent manner, and apparently slowed I activation. In current-clamp recordings, sevoflurane significantly decreased spike firing during the rebound activation, which is essential for responses to the sensory inputs from the cortex and thalamus. The sevoflurane-induced inhibition of I in striatal cholinergic interneurons may lead to alterations of the acetylcholine-dopamine balance in the neural circuits during the early postnatal period.