The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.T...The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.展开更多
Inwardly rectifying potassium(Kir)channels make it easier for K^(+)to enter into a cell and subsequently regulate cellular biological functions.Kir5.1(encoded by KCNJ16)alone can form a homotetramer and can form heter...Inwardly rectifying potassium(Kir)channels make it easier for K^(+)to enter into a cell and subsequently regulate cellular biological functions.Kir5.1(encoded by KCNJ16)alone can form a homotetramer and can form heterotetramers with Kir4.1(encoded by KCNJ10)or Kir4.2(encoded by KCNJ15).In most cases,homomeric Kir5.1 is non-functional,while hetero-meric Kir5.1 on the cell membrane contributes to the inward flow of K^(+)ions,which can be regulated by intracellular pH and a variety of signaling mechanisms.In the form of a heterotetramer,Kir5.1 regulates Kir4.1/4.2 activity and is involved in the maintenance of nephron function.Actually,homomeric Kir5.1 may also play a very important role in diseases,including in the ventilatory response to hypoxia and hypercapnia,hearing impairment,cardio-vascular disease and cancer.With an increase in the number of studies into the roles of Kir channels,researchers are paying more attention to the pathophysiological functions of Kir5.1.This minireview provides an overview regarding these Kir5.1 roles.展开更多
基金supported by the National Natural Science Foundation of China(31971058 and 31571174)the Youth Fund for Scientific and Technological Research in Higher Education Institutions of Hebei Province(QN2019019)the Youth Science and Technology Talent Support Program of Natural Science in Hebei Medical University(CYQD201907)。
文摘The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.
文摘Inwardly rectifying potassium(Kir)channels make it easier for K^(+)to enter into a cell and subsequently regulate cellular biological functions.Kir5.1(encoded by KCNJ16)alone can form a homotetramer and can form heterotetramers with Kir4.1(encoded by KCNJ10)or Kir4.2(encoded by KCNJ15).In most cases,homomeric Kir5.1 is non-functional,while hetero-meric Kir5.1 on the cell membrane contributes to the inward flow of K^(+)ions,which can be regulated by intracellular pH and a variety of signaling mechanisms.In the form of a heterotetramer,Kir5.1 regulates Kir4.1/4.2 activity and is involved in the maintenance of nephron function.Actually,homomeric Kir5.1 may also play a very important role in diseases,including in the ventilatory response to hypoxia and hypercapnia,hearing impairment,cardio-vascular disease and cancer.With an increase in the number of studies into the roles of Kir channels,researchers are paying more attention to the pathophysiological functions of Kir5.1.This minireview provides an overview regarding these Kir5.1 roles.
