KCa1.1 β4-subunits are not responsible for iberiotoxin-resistance in baroreceptor neurons in adult male rats

doi:10.1016/j.ijcard.2014.10.128

International Journal of Cardiology

Volume 178, 15 January 2015, Pages 184-187

https://doi.org/10.1016/j.ijcard.2014.10.128 Get rights and content

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Conflict of interests

The authors have declared that no competing interest exists.

Acknowledgment

This project was supported by research grants from the National Natural Science Foundation of China (81173051; 31171122; 31400983).

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Cited by (11)

Estrogen-dependent MicroRNA-504 Expression and Related Baroreflex Afferent Neuroexcitation via Negative Regulation on KCNMB4 and KCa1.1 β4-subunit Expression
2020, Neuroscience
Citation Excerpt :
Finally, there is almost no distribution of myelinated Ah-types in adult males except for A- and C-types (Li and Schild, 2007; Li et al., 2008). Therefore, single-cell qRT-PCR tests (Li et al., 2015; Xu et al., 2015; Liu et al., 2016) were carried out using electrophysiologically and morphometrically identified individual BRNs (Li and Schild, 2007; Lu et al., 2013) (Fig. 6A) isolated from adult female rats underwent aortic depressor nerve (ADN) fluorescent dye (Dil) labeling to identify the baroreceptor phenotype (Lu et al., 2013). These data indicated that myelinated A-, Ah- and unmyelinated C-type BRNs expressed both α- (n = 9/17, 8/10, and 11/13, respectively, for each category) and β4-subunits (n = 7/13, 8/9, and 10/11, respectively) (Fig. S8) and the percentage of positive qRT-PCR detection was 52.9%, 80.0%, and 84.6% for α-subunits and 53.8%, 88.9%, and 83.3% for β4-subunits, respectively, suggesting that less population of A-types expresses both subunits (Fig. 6B-C).
Large conductance of Ca²⁺-activated K⁺ channel (KCa1.1) plays an inhibitory role in neuroexcitation. However, the expression of KCNMB4/β4-subunit in the nodose ganglia (NG) and nucleus tractus solitarius (NTS), and its effect and regulation on baroreflex afferent function at post-transcriptional level of female rats remains unknown. Here, we demonstrated that the expression of β4-subunit encoded by KCNMB4 was significantly lower in females vs. males and ovariectomized (OVX) rats in the NG. Although all baroreceptor neurons (BRNs) expressed β4-subunit, altered discharge characteristics were only observed in Ah-type neurons after ovariectomy. Notably, the decreased excitability of Ah-types was restored by paxilline and further enhanced by iberiotoxin. The consistent changes were observed in excitatory post-synaptic currents. The level of miR-504 was higher in females, which was predicted to bind to the 3′UTR of KCNMB4. In consistent, an inverse expression pattern between miR-504 and KCNMB4 was observed in baroreflex afferents. The paxilline-sensitive β4-subunits is less in Ah-types and up-regulated by ovariectomy. These data indicated that KCa1.1 β4-subunit is the key regulator in neuroexcitation of Ah-types and sexual-dimorphism in baroreflex afferent function through estrogen-dependent inhibition of KCNMB4 expression via miR-504.
FGF-21 ameliorates essential hypertension of SHR via baroreflex afferent function
2020, Brain Research Bulletin
Hypertension is a common complication of metabolic abnormalities associated with cardiovascular system and characterized by sexual dimorphism in mammals. Fibroblast growth factor-21 (FGF-21) plays a critical role in metabolic-disorder related hypertension through the afferent loop of baroreflex. However, the gender difference in FGF-21-mediated blood pressure (BP) regulation via sexual dimorphic expression of FGFRs in the nodose (NG) and nucleus tractus solitarius (NTS) were not elucidated in physiological and genomic form of hypertension. The gene and protein expression of FGFRs were tested by qRT-PCR, immunoblotting and immunostaining; the serum level of FGF21 was tested using ELISA; The BP was monitored while FGF21 was nodose microinjected. The results showed that more potent BP reduction was confirmed in female vs. male rats by nodose microinjection of rhFGF-21 along with higher expression of FGFR2 and FGFR4 in the nodose compared with age-match male and ovariectomized (OVX) rats, rather than other receptor subtypes, which is consistent well with immunohistochemical analysis. Additionally, serum FGF-21 was significantly higher in female-WKY, and this level of FGF-21 was dramatically declined in spontaneous hypertensive rats (SHR) with significant down-regulation of FGFR1/R4 for male-SHR and FGFR2/FGFR4 for female-SHR, respectively. Apparently, high BP of SHR of either sex could be reduced by rhFGF-21 nodose microinjection. These data extends our current understanding that sexual-specific distribution/expression of FGF-21/FGFRs is likely to contribute at least partially to sexual dimorphism of baroreflex afferent function on BP regulation in rats. FGF-21-mdiated BP reduction sheds new light on clinical management of primary/genomic form of hypertension.
KCa1.1-mediated frequency-dependent central and peripheral neuromodulation via Ah-type baroreceptor neurons located within nodose ganglia and nucleus of solitary tract of female rats
2015, International Journal of Cardiology
KCa1.1 is potential marker for distinguishing Ah-type baroreceptor neurons in NTS and contributes to sex-specific presynaptic neurotransmission in baroreflex afferent pathway
2015, Neuroscience Letters
Citation Excerpt :
Following the classification, the stimulation from a concentric bipolar electrode (Fig. 1B, indicated by▾) was applied and solitary track-evoked EPSCs were also recorded in Cap-insensitive (presumable A-type) NTS neurons before and after 100 nM iberiotoxin (IbTX), a selective KCa1.1 channel blocker, on top of CTZ. The results (Fig. 1B) showed that the peak, DTC, and AUC were dramatically increased in the presence of CTZ but was not further enhanced by IbTX (Fig. 1B–E), suggesting, in accordance with our previous data collected from the 1st-order neurons [2,8], that the myelinated/Cap-insensitive afferent does not contribute to the enhanced neurotransmission by increasing glutamate release via blocking KCa1.1 channel. In the case of Cap-sensitive NTS (presumable C-type) neurons, the hyperpolarization induced a significant delay excitation (Fig. 2A, indicated by ) and the peak, DTC, and AUC were all further increased (P < 0.05 or P < 0.01 vs CTZ alone) in the presence of 100 nM IbTX after initial increases by removing the rapid desensitization with 100 μM CTZ (Fig. 2B–E), These results suggest that blocking KCa1.1 play a role in unmyelinated neurotransmission and markedly enhance the excitatory neurotransmission by upregulation of pre-synaptic release of glutamate.
Sexual-dimorphic neurocontrol of circulation has been described in baroreflex due largely to the function of myelinated Ah-type baroreceptor neurons (BRNs, 1st-order) in nodose. However, it remains unclear if sex- and afferent-specific neurotransmission could also be observed in the central synapses within nucleus of solitary track (NTS, 2nd-order). According to the principle of no mixed neurotransmission among afferents and differentiation of Ah- and A-types to iberiotoxin (IbTX) observed in nodose, the 2nd-order Ah-type BRNs are highly expected. To test this hypothesis, the excitatory post-synaptic currents (EPSCs) were recorded in identified 2nd-order BRNs before and after IbTX using brain slice and whole-cell patch. These results showed that, in male rats, the dynamics of EPSCs in capsaicin-sensitive C-types were dramatically altered by IbTX, but not in capsaicin-insensitive A-types. Interestingly, near 50% capsaicin-insensitive neurons in females showed similar effects to C-types, suggesting the existence of Ah-types in NTS, which may be the likely reason why the females had lower blood pressure and higher sensitivity to aortic depressor nerve stimulation via KCa1.1-mediated presynaptic glutamate release from Ah-type afferent terminals.
Estrogen-dependent KCa1.1 modulation is essential for retaining neuroexcitation of female-specific subpopulation of myelinated Ah-type baroreceptor neurons in rats
2021, Acta Pharmacologica Sinica
Perfect cellular platform for electrophysiology: Acutely isolated vagal ganglion neurons from adult canines
2020, Chinese Journal of Pharmacology and Toxicology

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¹: These authors contributed equally to this work.

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Letter to the EditorKCa1.1 β4-subunits are not responsible for iberiotoxin-resistance in baroreceptor neurons in adult male rats

Section snippets

Conflict of interests

Acknowledgment

First page preview

Int. J. Cardiol.

Mol. Pain

Brain Res.

Neurosci. Lett.

FEBS Lett.

Int. J. Cardiol.

Letter to the Editor
KCa1.1 β4-subunits are not responsible for iberiotoxin-resistance in baroreceptor neurons in adult male rats