GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro

Glucagon-like peptide-1 (GLP-1) is mainly secreted by preglucagonergic neurons in the nucleus tractus solitarius, which plays critical roles in regulation of neuronal activity in the central nervous system through its receptor. In the cerebellar cortex, GLP-1 receptor is abundantly expressed in the...

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Main Authors: Yang Liu, Li-Xin Cao, Wei-Yao Wang, Yong-Rui Piao, Jun-Ya Wang, Chun-Ping Chu, Yan-Hua Bing, De-Lai Qiu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2023.1126447/full
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author Yang Liu
Li-Xin Cao
Wei-Yao Wang
Yong-Rui Piao
Yong-Rui Piao
Jun-Ya Wang
Chun-Ping Chu
Yan-Hua Bing
De-Lai Qiu
De-Lai Qiu
author_facet Yang Liu
Li-Xin Cao
Wei-Yao Wang
Yong-Rui Piao
Yong-Rui Piao
Jun-Ya Wang
Chun-Ping Chu
Yan-Hua Bing
De-Lai Qiu
De-Lai Qiu
author_sort Yang Liu
collection DOAJ
description Glucagon-like peptide-1 (GLP-1) is mainly secreted by preglucagonergic neurons in the nucleus tractus solitarius, which plays critical roles in regulation of neuronal activity in the central nervous system through its receptor. In the cerebellar cortex, GLP-1 receptor is abundantly expressed in the molecular layer, Purkinje cell (PC) layer and granular layer, indicating that GLP-1 may modulate the cerebellar neuronal activity. In this study, we investigated the mechanism by which GLP1 modulates mouse cerebellar PC activity in vitro. After blockade of glutamatergic and GABAergic synaptic transmission in PCs, GLP1 increased the spike firing rate accompanied by depolarization of membrane potential and significantly depressed the after-hyperpolarizing potential and outward rectifying current of spike firing discharges via GLP1 receptors. In the presence of TTX and Ba2+, GLP1 significantly enhanced the hyperpolarized membrane potential-evoked instant current, steady current, tail current (I-tail) and hyperpolarization-activated (IH) current. Application of a selective IH channel antagonist, ZD7288, blocked IH and abolished the effect of GLP1 on PC membrane currents. The GLP1 induced enhancement of membrane currents was also abolished by a selective GLP1 receptor antagonist, exendin-9-39, as well as by protein kinase A (PKA) inhibitors, KT5720 and H89. In addition, immunofluorescence detected GLP1 receptor in the mouse cerebellar cortex, mostly in PCs. These results indicated that GLP1 receptor activation enhanced IH channel activity via PKA signaling, resulting in increased excitability of mouse cerebellar PCs in vitro. The present findings indicate that GLP1 plays a critical role in modulating cerebellar function by regulating the spike firing activity of mouse cerebellar PCs.
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spelling doaj.art-4832b497e453412ea5edad9c15b942372023-04-05T04:22:17ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-04-011610.3389/fnmol.2023.11264471126447GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitroYang Liu0Li-Xin Cao1Wei-Yao Wang2Yong-Rui Piao3Yong-Rui Piao4Jun-Ya Wang5Chun-Ping Chu6Yan-Hua Bing7De-Lai Qiu8De-Lai Qiu9Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin, ChinaDepartment of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin, ChinaDepartment of Physiology, College of Basic Medicine, Jilin Medical University, Jilin, Jilin, ChinaDepartment of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin, ChinaDepartment of Urology, Affiliated Hospital of Yanbian University, Yanji, Jilin, ChinaDepartment of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin, ChinaDepartment of Physiology, College of Basic Medicine, Jilin Medical University, Jilin, Jilin, ChinaFunctional Experiment Center, College of Medicine, Yanbian University, Yanji, Jilin, ChinaDepartment of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin, ChinaDepartment of Physiology, College of Basic Medicine, Jilin Medical University, Jilin, Jilin, ChinaGlucagon-like peptide-1 (GLP-1) is mainly secreted by preglucagonergic neurons in the nucleus tractus solitarius, which plays critical roles in regulation of neuronal activity in the central nervous system through its receptor. In the cerebellar cortex, GLP-1 receptor is abundantly expressed in the molecular layer, Purkinje cell (PC) layer and granular layer, indicating that GLP-1 may modulate the cerebellar neuronal activity. In this study, we investigated the mechanism by which GLP1 modulates mouse cerebellar PC activity in vitro. After blockade of glutamatergic and GABAergic synaptic transmission in PCs, GLP1 increased the spike firing rate accompanied by depolarization of membrane potential and significantly depressed the after-hyperpolarizing potential and outward rectifying current of spike firing discharges via GLP1 receptors. In the presence of TTX and Ba2+, GLP1 significantly enhanced the hyperpolarized membrane potential-evoked instant current, steady current, tail current (I-tail) and hyperpolarization-activated (IH) current. Application of a selective IH channel antagonist, ZD7288, blocked IH and abolished the effect of GLP1 on PC membrane currents. The GLP1 induced enhancement of membrane currents was also abolished by a selective GLP1 receptor antagonist, exendin-9-39, as well as by protein kinase A (PKA) inhibitors, KT5720 and H89. In addition, immunofluorescence detected GLP1 receptor in the mouse cerebellar cortex, mostly in PCs. These results indicated that GLP1 receptor activation enhanced IH channel activity via PKA signaling, resulting in increased excitability of mouse cerebellar PCs in vitro. The present findings indicate that GLP1 plays a critical role in modulating cerebellar function by regulating the spike firing activity of mouse cerebellar PCs.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1126447/fullglucagon-like peptide-1 (GLP-1)cerebellar Purkinje cellwhole-cell patch-clamp recordinghyperpolarization-activated current (IH)protein kinase A
spellingShingle Yang Liu
Li-Xin Cao
Wei-Yao Wang
Yong-Rui Piao
Yong-Rui Piao
Jun-Ya Wang
Chun-Ping Chu
Yan-Hua Bing
De-Lai Qiu
De-Lai Qiu
GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro
Frontiers in Molecular Neuroscience
glucagon-like peptide-1 (GLP-1)
cerebellar Purkinje cell
whole-cell patch-clamp recording
hyperpolarization-activated current (IH)
protein kinase A
title GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro
title_full GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro
title_fullStr GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro
title_full_unstemmed GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro
title_short GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro
title_sort glp 1 enhances hyperpolarization activated currents of mouse cerebellar purkinje cell in vitro
topic glucagon-like peptide-1 (GLP-1)
cerebellar Purkinje cell
whole-cell patch-clamp recording
hyperpolarization-activated current (IH)
protein kinase A
url https://www.frontiersin.org/articles/10.3389/fnmol.2023.1126447/full
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