ERG Channels Regulate Excitability in Stellate and Bushy Cells of Mice Ventral Cochlear Nucleus

Yıldırım, Caner; Bal, Ramazan

doi:10.1007/s00232-018-0048-5

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…The I K(erg) is inherent in neurons or different types of electrically excitable cells, such as endocrine or neuroendocrine cells. It can significantly affect the maintenance of the resting membrane potential and the modifications in sub-threshold excitability [18][19][20], thereby leading to significant changes in the discharge rate of spontaneous action potentials [21,22]. Consequently, the resultant perturbations in these KV channels' activity have the propensity to modify the stimulus-secretion coupling of these cells [23].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Synergistic Inhibition of IK(erg) and IK(DR) by Ribociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor

Liu

Chang

2020

IJMS

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Ribociclib (RIB, LE011, Kisqali®), an orally administered inhibitor of cyclin-dependent kinase-4/6 (CDK-4/6) complex, is clinically effective for the treatment of several malignancies, including advanced breast cancer. However, information regarding the effects of RIB on membrane ion currents is limited. In this study, the addition of RIB to pituitary tumor (GH3) cells decreased the peak amplitude of erg-mediated K+ current (IK(erg)), which was accompanied by a slowed deactivation rate of the current. The IC50 value for RIB-perturbed inhibition of deactivating IK(erg) in these cells was 2.7 μM. In continued presence of μM RIB, neither the subsequent addition of 17β-estradiol (30 μM), phorbol 12-myristate 13-acetate (10 μM), or transforming growth factor-β (1 μM) counteracted the inhibition of deactivating IK(erg). Its presence affected the decrease in the degree of voltage-dependent hysteresis for IK(erg) elicitation by long-duration triangular ramp voltage commands. The presence of RIB differentially inhibited the peak or sustained component of delayed rectifier K+ current (IK(DR)) with an effective IC50 of 28.7 or 11.4 μM, respectively, while it concentration-dependently decreased the amplitude of M-type K+ current with IC50 of 13.3 μM. Upon 10-s long membrane depolarization, RIB elicited a decrease in the IK(DR) amplitude, which was concomitant with an accelerated inactivation time course. However, the inability of RIB (10 μM) to modify the magnitude of the hyperpolarization-activated cation current was disclosed. The mean current–voltage relationship of IK(erg) present in HL-1 atrial cardiomyocytes was inhibited in the presence of RIB (10 μM). Collectively, the hyperpolarization-activated cation current was observed. RIB-mediated perturbations in ionic currents presented herein are upstream of its suppressive action on cytosolic CDK-4/6 activities and partly participates in its modulatory effects on the functional activities of pituitary tumor cells (e.g., GH3 cells) or cardiac myocytes (e.g., HL-1 cells).

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Section: Introductionmentioning

confidence: 99%

Characterization of the Synergistic Inhibition of IK(erg) and IK(DR) by Ribociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor

Liu

Chang

2020

IJMS

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“…The downregulation of Kcnh7 gene expression was found in PV and SST neurons in Shank3 KO mice, a model of autism primarily associated with excitatory synaptic dysfunction in projection neurons. As KCNH7 serves as an inward rectifying potassium channel crucial for regulating neuronal excitability 52,67 , the downregulation of its expression could result in heightened excitability in PV and SST neurons (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

Distinct functions of parvalbumin and somatostatin interneurons in the anterior cingulate cortex result in heterogeneity of social interaction impairments

Wu,

Qi,

Sima

et al. 2024

Preprint

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The anterior cingulate cortex (ACC) serves as a core region in social networks, and impairments in this area have been identified in autism spectrum disorders. Our prior research demonstrated that deficits in pyramidal neurons in ACC adversely impacted mouse social interaction. The preservation of functional output in the ACC by pyramidal neurons relies on the dynamic regulation by the different types of interneurons. However, the precise regulatory roles of distinct interneurons within the ACC in shaping social interaction have hitherto remained largely enigmatic. In this study, we elucidated the involvement of parvalbumin (PV) and somatostatin (SST) interneurons within the ACC in modulating social interaction behavior. Specifically, we ascertain that PV interneurons play a more prominent role in initiating sociability, whereas SST interneurons uniquely influence social preference. Notably, the downregulation of the autism high-risk gene Kcnh7 is identified in both PV and SST interneurons within the Shank3 knockout (KO) autistic mouse model. Further, the selective KO of Kcnh7 in PV- or SST-positive neurons contributes to disruptions in sociability and social preference, respectively. The divergent modulation of social interaction by PV and SST interneurons in the ACC is attributed to the distinct input received by these neuronal subtypes. Our findings offer nuanced insights into the multifaceted roles of PV and SST neurons within the ACC in the context of social interaction, contributing to a comprehensive understanding of the neurobiological underpinnings of social behavior disorders in autism. The delineation of these mechanisms is imperative for advancing our comprehension of the etiological basis of autism, thereby paving the way for novel avenues of research aimed at addressing the heterogeneous phenotypes associated with social interaction dysfunction in cortical interneurons.

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“…Several studies showed a role of ERG channels in the nervous system ( Sacco et al, 2003 ; Niculescu et al, 2013 ). In ventral cochlear nucleus neurons, they play a role in setting AP threshold and AP frequency ( Yildirim and Bal, 2018 ). In the mouse MNTB, where ERG1 and ERG3 subunits are predominant, ERG currents modulate Kv1 currents and limit AP generation around AP threshold voltages ( Hardman and Forsythe, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

Maraslioglu-Sperber,

Pizzi,

Fisch

et al. 2024

Front. Cell. Neurosci.

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The lateral superior olive (LSO), a prominent integration center in the auditory brainstem, contains a remarkably heterogeneous population of neurons. Ascending neurons, predominantly principal neurons (pLSOs), process interaural level differences for sound localization. Descending neurons (lateral olivocochlear neurons, LOCs) provide feedback into the cochlea and are thought to protect against acoustic overload. The molecular determinants of the neuronal diversity in the LSO are largely unknown. Here, we used patch-seq analysis in mice at postnatal days P10-12 to classify developing LSO neurons according to their functional and molecular profiles. Across the entire sample (n = 86 neurons), genes involved in ATP synthesis were particularly highly expressed, confirming the energy expenditure of auditory neurons. Two clusters were identified, pLSOs and LOCs. They were distinguished by 353 differentially expressed genes (DEGs), most of which were novel for the LSO. Electrophysiological analysis confirmed the transcriptomic clustering. We focused on genes affecting neuronal input–output properties and validated some of them by immunohistochemistry, electrophysiology, and pharmacology. These genes encode proteins such as osteopontin, Kv11.3, and Kvβ3 (pLSO-specific), calcitonin-gene-related peptide (LOC-specific), or Kv7.2 and Kv7.3 (no DEGs). We identified 12 “Super DEGs” and 12 genes showing “Cluster similarity.” Collectively, we provide fundamental and comprehensive insights into the molecular composition of individual ascending and descending neurons in the juvenile auditory brainstem and how this may relate to their specific functions, including developmental aspects.

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ERG Channels Regulate Excitability in Stellate and Bushy Cells of Mice Ventral Cochlear Nucleus

Cited by 11 publications

References 36 publications

Characterization of the Synergistic Inhibition of IK(erg) and IK(DR) by Ribociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor

Characterization of the Synergistic Inhibition of IK(erg) and IK(DR) by Ribociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor

Distinct functions of parvalbumin and somatostatin interneurons in the anterior cingulate cortex result in heterogeneity of social interaction impairments

Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

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