PARK, CHEONG DAHM Kim, Jong-Hyun Yoon, Bo-Eun Choi, Eui-Ju Lee, C. Justin Shin, Hee-Sup 2024-01-20T19:00:45Z 2024-01-20T19:00:45Z 2021-09-04 2010-08 0027-8424 https://pubs.kist.re.kr/handle/201004/131228 Endogenous opioids generate analgesic signals in the periaqueductal gray (PAG). However, because cell types in the PAG are difficult to identify, its neuronal mechanism has remained poorly understood. To address this issue, we characterized PAG neurons by their electrical properties using differentially labeled GABAergic and output neurons in the PAG. We found that GABAergic neurons were mostly fast-spiking cells and could be further divided into two distinct classes: with or without low-threshold spikes (LTS) driven by T-type channels. In contrast, the PAG output neurons lacked LTS and showed heterogeneous firing patterns. To reveal the function of the LTS, we examined the mutant mice lacking the alpha 1G T-type channels (alpha 1G(-/-)). The mutant mice lacked LTS in the fast-spiking GABAergic neurons of the PAG and unexpectedly showed impaired opioid-dependent analgesia; a similar phenotype was reproduced in PAG-specific alpha 1G-knockdown mice. Electrophysiological analyses revealed functional expression of mu-opioid receptors in the low threshold-spiking GABAergic neurons. These neurons in the mutant lacking LTS showed markedly enhanced discharge activities, which led to an augmented inhibition of output neurons. Furthermore, the impaired analgesia observed in alpha 1G(-/-) mice was reversed by blocking local GABA(A) receptors. These results indicate that alpha 1G T-type channels are critical for the opioidergic descending analgesia system in the PAG. English NATL ACAD SCIENCES T-type channels control the opioidergic descending analgesia at the low threshold-spiking GABAergic neurons in the periaqueductal gray Article 10.1073/pnas.1009532107 1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.107, no.33, pp.14857 - 14862 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 107 33 14857 14862 N scie scopus 000281287600061 2-s2.0-77957095286 Multidisciplinary Sciences Science & Technology - Other Topics Article CALCIUM-CHANNELS CA2+ CHANNELS GUINEA-PIG MORPHINE ANALGESIA ACTION-POTENTIALS PAIN INHIBITION NERVOUS-SYSTEM RAT INVITRO BRAIN opioid-descending analgesia alpha 1G morphine stress calcium-activated potassium channel afterhyperpolarization