Modulation of hyperpolarization-activated cation current Ih by volatile anesthetic sevoflurane in the mouse striatum
Yusuke Sugasawa1, Masataka Fukuda1, Nozomi Ando1
1Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Neurophysiology Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
Abstract:
Volatile anesthetics have been reported to inhibit hyperpolarization-activated cyclic-nucleotide gated channels underlying the hyperpolarization-activated cation current (Ih) that contributes to generation of synchronized oscillatory neural rhythms. Meanwhile, the developmental change of Ih 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 Ih and on functional Ih activation kinetics of cholinergic interneurons in developing striatum. Our analyses showed that the changes in Ih of cholinergic interneurons occurred in conjunction with maturation. Sevoflurane application (1-4%) caused significant inhibition of Ih in a dose-dependent manner, and apparently slowed Ih 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 Ih in striatal cholinergic interneurons may lead to alterations of the acetylcholine-dopamine balance in the neural circuits during the early postnatal period.
