Isoflurane, but Not the Nonimmobilizers F6 and F8, Inhibits Rat Spinal Cord Motor Neuron CaV1 Calcium Currents

Abstract

Background Volatile anesthetics decrease Ca2+ entry through voltage-dependent Ca2+ channels. Ca2+ influences neurotransmitter release and neuronal excitability. Because volatile anesthetics act specifically on the spinal cord to produce immobility, we examined the effect of isoflurane and the nonimmobilizers F6 (1, 2- dichlorohexafluorocyclobutane) and F8 (2, 3- dichlorooctafluorobutane) on CaV1 and CaV2 Ca2+ channels in spinal cord motor neurons and dorsal root ganglion neurons. Methods Using patch clamping, we compared the effects of isoflurane with those of F6 and F8 on CaV1 and CaV2 channels in isolated, cultured adult rat spinal cord motor neurons and on CaV1 and CaV2 channels in adult rat dorsal root ganglion sensory neurons. Results In spinal cord motor neurons, isoflurane, but not F6 or F8, inhibited currents through CaV1 channels. Isoflurane and at least one of the nonimmobilizers inhibited currents through CaV1 and CaV2 channels in dorsal root ganglion neurons and Cav2 in spinal cord motor neurons Conclusion The findings that isoflurane, but not nonimmobilizers, inhibited CaV1 Ca2+ channels in spinal cord motor neurons are consistent with the notion that spinal cord motor neurons might mediate isoflurane-induced immobility. Additional studies are required to examine whether inhibition of CaV1 calcium currents in spinal cord motor neurons are sufficient, or whether actions on other channels/proteins also contribute to isoflurane-induced immobility.

Identifying c-fos Expression as a Strategy to Investigate the Actions of General Anesthetics on the Central Nervous System

“…Isoflurane (1.2%, 2 h) and halothane (1.0%, 2 h) significantly increased the expression of c-fos in the GABAergic neurons within the VLPO and decreased c-fos expression in the non-GABAergic neurons, whereas the non-immobilizer 1,2-dichlorohexafluorocyclobutane (F6) failed to affect the c-fos expression of VLPO, indicating that activation of GABAergic subpopulation neurons within the VLPO may be relevant to volatile anesthetic-induced unconsciousness [ 26 ]. Theoretically, the molecular targets that are sensitive to volatile anesthetics but not to the non-immobilizer, such as presynaptic voltage-gated sodium channel (Na v ) [ 27 ] and voltage-gated calcium channel (Ca v ) [ 28 ], are the underlying targets for volatile anesthetics to increase c-fos expression in GABAergic neurons of VLPO. This is likely due to presynaptic inhibition that increases glutamate release in the VLPO neurons.…”

The Effects of General Anesthetics on Synaptic Transmission

“…For neuronal L-type Ca v , halothane can reduce L-type currents in human neuronal cells primarily by decreasing the channel opening and enhancing the rate for channel closing and inactivation [ 148 ]. Isoflurane at concentration of 0.6 mM (~2 MAC) can inhibit Ca v 1.1 and Ca v 1.2 channels but not the non-immobilizer F6 in isolated cultured adult rat spinal cord motor neurons, suggesting that these channels may contribute to isoflurane-induced immobility [ 149 ]. Halothane (0.45 and 0.9 mM), isoflurane (0.54 and 1.23 mM), and enflurane (0.65 and 1.48 mM) reduce L-type Ca v peak currents to a similar extent, but do not shift the current-voltage (I-V) relationship for L-type current activation [ 150 ].…”