KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock

Abstract The suprachiasmatic nucleus (SCN) central clock comprises two coupled oscillators, with light entraining the retinorecipient vasoactive intestinal peptide (VIP)-positive ventrolateral oscillator, which then entrains the arginine vasopressin (AVP)-positive dorsomedial oscillator. While gluco...

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Autores principales:	Jyh-Jeen Yang, Ruo-Ciao Cheng, Pi-Cheng Cheng, Yi-Chi Wang, Rong-Chi Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f9e81018f664440f9f4f162588a2e699
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spelling	oai:doaj.org-article:f9e81018f664440f9f4f162588a2e6992021-12-02T11:41:12ZKATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock10.1038/s41598-017-00699-32045-2322https://doaj.org/article/f9e81018f664440f9f4f162588a2e6992017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00699-3https://doaj.org/toc/2045-2322Abstract The suprachiasmatic nucleus (SCN) central clock comprises two coupled oscillators, with light entraining the retinorecipient vasoactive intestinal peptide (VIP)-positive ventrolateral oscillator, which then entrains the arginine vasopressin (AVP)-positive dorsomedial oscillator. While glucose availability is known to alter photic entrainment, it is unclear how the SCN neurones respond to metabolic regulation and whether the two oscillators respond differently. Here we show that the ATP-sensitive K+ (KATP) channel mediates differential responses to glucose shortage of the two oscillators. RT-PCR and electrophysiological results suggested the presence of Kir6.2/SUR1 KATP channels in the SCN neurones. Immunostaining revealed preferential distribution of Kir6.2 in the dorsomedial subregion and selective colocalization with AVP. Whole cell recordings with ATP-free pipette solution indicated larger tolbutamide-induced depolarisation and tolbutamide-sensitive conductance in dorsal SCN (dSCN) than ventral SCN (vSCN) neurones. Tolbutamide-sensitive conductance was low under perforated patch conditions but markedly enhanced by cyanide inhibition of mitochondrial respiration. Glucoprivation produced a larger steady-state inhibition in dSCN than vSCN neurones, and importantly hypoglycemia via opening KATP channels selectively inhibited the KATP-expressing neurones. Our results suggest that the AVP-SCN oscillator may act as a glucose sensor to respond to glucose shortage while sparing the VIP-SCN oscillator to remain in synch with external light-dark cycle.Jyh-Jeen YangRuo-Ciao ChengPi-Cheng ChengYi-Chi WangRong-Chi HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jyh-Jeen Yang Ruo-Ciao Cheng Pi-Cheng Cheng Yi-Chi Wang Rong-Chi Huang KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock
description	Abstract The suprachiasmatic nucleus (SCN) central clock comprises two coupled oscillators, with light entraining the retinorecipient vasoactive intestinal peptide (VIP)-positive ventrolateral oscillator, which then entrains the arginine vasopressin (AVP)-positive dorsomedial oscillator. While glucose availability is known to alter photic entrainment, it is unclear how the SCN neurones respond to metabolic regulation and whether the two oscillators respond differently. Here we show that the ATP-sensitive K+ (KATP) channel mediates differential responses to glucose shortage of the two oscillators. RT-PCR and electrophysiological results suggested the presence of Kir6.2/SUR1 KATP channels in the SCN neurones. Immunostaining revealed preferential distribution of Kir6.2 in the dorsomedial subregion and selective colocalization with AVP. Whole cell recordings with ATP-free pipette solution indicated larger tolbutamide-induced depolarisation and tolbutamide-sensitive conductance in dorsal SCN (dSCN) than ventral SCN (vSCN) neurones. Tolbutamide-sensitive conductance was low under perforated patch conditions but markedly enhanced by cyanide inhibition of mitochondrial respiration. Glucoprivation produced a larger steady-state inhibition in dSCN than vSCN neurones, and importantly hypoglycemia via opening KATP channels selectively inhibited the KATP-expressing neurones. Our results suggest that the AVP-SCN oscillator may act as a glucose sensor to respond to glucose shortage while sparing the VIP-SCN oscillator to remain in synch with external light-dark cycle.
format	article
author	Jyh-Jeen Yang Ruo-Ciao Cheng Pi-Cheng Cheng Yi-Chi Wang Rong-Chi Huang
author_facet	Jyh-Jeen Yang Ruo-Ciao Cheng Pi-Cheng Cheng Yi-Chi Wang Rong-Chi Huang
author_sort	Jyh-Jeen Yang
title	KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock
title_short	KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock
title_full	KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock
title_fullStr	KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock
title_full_unstemmed	KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock
title_sort	katp channels mediate differential metabolic responses to glucose shortage of the dorsomedial and ventrolateral oscillators in the central clock
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f9e81018f664440f9f4f162588a2e699
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KATP Channels Mediate Differential Metabolic Responses to Glucose Shortage of the Dorsomedial and Ventrolateral Oscillators in the Central Clock

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