Isoflurane causes muscle contraction in Drosophila melanogaster despite inducing hyperpolarized state

Isoflurane is a commonly used volatile anesthetic; however, its mechanisms are not well characterized. To better understand mechanisms of action, isoflurane was applied to model larval Drosophila muscle preparations. Membrane potential, evoked transmissions, and observations of muscle behavior were recorded. Muscle contraction was not inhibited by dantrolene (10 mM) or ryanodine (100 µM). Thapsigargin (1 mM), which depleted the sarcoplasmic reticulum of Ca ²⁺ , inhibited muscle contraction. Blebbistatin blocked contractions induced by isoflurane, allowing for membrane hyperpolarization. Isoflurane releases stored intracellular calcium from the sarcoplasmic reticulum of the skeletal muscle, causing muscle contraction despite direct hyperpolarization of the membrane.