Estrogen-dependent KCa1.1 modulation is essential for retaining neuroexcitation of female-specific subpopulation of myelinated Ah-type baroreceptor neurons in rats  

作　　者：Lu-qi Wang Zhao Qian Hai-lan Ma Meng Zhou Hu-die Li Chang-peng Cui Da-li Luo Xue-lian Li Bai-yan Li 

机构地区：[1]Department of Pharmacology,State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,and Key Laboratory of Cardiovascular Medicine Research,Ministry of Education,College of Pharmacy,Harbin Medical University,Harbin 150081,China [2]Department of Pharmacology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China [3]Department of Pharmacy,the First Affiliated Hospital of Harbin Medical University,Harbin 150010,China

出　　处：《Acta Pharmacologica Sinica》2021年第12期2173-2180,共8页中国药理学报（英文版）

基　　金：funded by National Natural Science Foundation of China(31171122,81573431,and 81971326)to BYL.

摘　　要：Female-specific subpopulation of myelinated Ah-type baroreceptor neurons(BRNs)in nodose ganglia is the neuroanatomical base of sexual-dimorphic autonomic control of blood pressure regulation,and KCa1.1 is a key player in modulating the neuroexcitation in nodose ganglia.In this study we investigated the exact mechanisms underlying KCa1.1-mediated neuroexcitation of myelinated Ah-type BRNs in the presence or absence of estrogen.BRNs were isolated from adult ovary intact(OVI)or ovariectomized(OVX)female rats,and identified electrophysiologically and fluorescently.Action potential(AP)and potassium currents were recorded using whole-cell recording.Consistently,myelinated Ah-type BRNs displayed a characteristic discharge pattern and significantly reduced excitability after OVX with narrowed AP duration and faster repolarization largely due to an upregulated iberiotoxin(IbTX)-sensitive component;the changes in AP waveform and repetitive discharge of Ah-types from OVX female rats were reversed by G1(a selective agonist for estrogen membrane receptor GPR30,100 nM)and/or IbTX(100 nM).In addition,the effect of G1 on repetitive discharge could be completely blocked by G15(a selective antagonist for estrogen membrane receptor GPR30,3μM).These data suggest that estrogen deficiency by removing ovaries upregulates KCa1.1 channel protein in Ah-type BRNs,and subsequently increases AP repolarization and blunts neuroexcitation through estrogen membrane receptor signaling.Intriguingly,this upregulated KCa1.1 predicted electrophysiologically was confirmed by increased mean fluorescent intensity that was abolished by estrogen treatment.These electrophysiological findings combined with immunostaining and pharmacological manipulations reveal the crucial role of KCa1.1 in modulation of neuroexcitation especially in female-specific subpopulation of myelinated Ah-type BRNs and extend our current understanding of sexual dimorphism of neurocontrol of BP regulation.

关 键 词：baroreflex afferent function neuroexcitation nodose ganglia estrogen membrane receptor GPR30 KCa1.1 IbTX G1 G15 whole-cell recording 

分 类 号：R96[医药卫生—药理学]