2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 3rd, 2025
Version: 4
Department of Neurobiology, Harvard Medical School
neuroscience
biorxiv

A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers

Stewart, R. G.Open in Google Scholar•Marquis, M. J.Open in Google Scholar•Jo, S.Open in Google Scholar•Harris, B.Open in Google Scholar•Aberra, A.Open in Google Scholar•Cook, V.Open in Google Scholar•Whiddon, Z.Open in Google Scholar•Yarov-Yarovoy, V.Open in Google Scholar•Ferns, M.Open in Google Scholar•Sack, J. T.Open in Google Scholar

KvS proteins are voltage-gated potassium channel subunits that form functional channels when assembled into heteromers with Kv2.1 (KCNB1) or Kv2.2 (KCNB2). Mammals have 10 KvS subunits: Kv5.1 (KCNF1), Kv6.1 (KCNG1), Kv6.2 (KCNG2), Kv6.3 (KCNG3), Kv6.4 (KCNG4), Kv8.1 (KCNV1), Kv8.2 (KCNV2), Kv9.1 (KCNS1), Kv9.2 (KCNS2), and Kv9.3 (KCNS3). Electrically excitable cells broadly express channels containing Kv2 subunits and most neurons have substantial Kv2 conductance. However, whether KvS subunits contribute to these conductances has not been clear, leaving the physiological roles of KvS subunits poorly understood. Here, we identify that two potent Kv2 inhibitors, used in combination, can distinguish conductances of Kv2/KvS heteromers and Kv2-only channels. We find that Kv5, Kv6, Kv8, or Kv9-containing channels are resistant to the Kv2-selective pore-blocker RY785 yet remain sensitive to the Kv2-selective voltage sensor modulator guangxitoxin-1E (GxTX). Using these inhibitors in mouse superior cervical ganglion neurons, we find predominantly RY785-sensitive conductances consistent with channels composed entirely of Kv2 subunits. In contrast, RY785-resistant but GxTX-sensitive conductances consistent with Kv2/KvS heteromeric channels predominate in mouse and human dorsal root ganglion neurons. These results establish an approach to pharmacologically distinguish conductances of Kv2/KvS heteromers from Kv2-only channels, enabling investigation of the physiological roles of endogenous KvS subunits. These findings suggest that drugs which distinguish KvS subunits could modulate electrical activity of subsets of Kv2-expressing cell types.

Similar Papers

biorxiv
Fri Apr 04 2025
Novel multi-transmitter calyx-like giant synapse revealed in the extended amygdala
The calyx of Held, a giant excitatory cup-like axo-somatic synapse, has been historically described exclusively in the auditory brainstem. Here, using PACAP immunohistochemistry combined with confocal and tomographic electron microscopy, we report the discovery of a morphologically similar calyx-like synapse in the extended amygdala of rodents, exhibiting unique neurochemical features. This previo...
Zhang, L.
•
Hernandez, V.
•
Giraldo, D. M.
•
Leon-Contreras, J. C.
...•
Eiden, L. E.
biorxiv
Fri Apr 04 2025
Purkinje cell branch morphology determines effect of inhibition and SK2 modulation on somatic pauses
Characterized by a highly complex branching of their dendrites, Purkinje cells (PCs) have a unique architecture that enables them to receive impressive amounts of sensorimotor information through their parallel fiber (PF) input. They are tasked to encode this information with high accuracy. In this work, we discuss the mechanisms through which PCs encode this information, and we show how they mult...
Chou, P.-J.
•
De Schutter, E.
•
Cirtala, G.
biorxiv
Thu Apr 03 2025
Mapping the coupling between tract reachability and cortical geometry of the human brain
The study of cortical geometry and connectivity is prevalent in research on the human brain. However, these two aspects of brain structure are usually examined separately, leaving the essential connections between the brain\'s folding patterns and white matter connectivity unexplored. In this study, we aimed to elucidate fundamental links between cortical geometry and white matter tract connectivi...
Li, D.
•
Zalesky, A.
•
Wang, Y.
•
Wang, H.
...•
Fan, L.
biorxiv
Thu Apr 03 2025
Common and distinct neural mechanisms of aversive and appetitive pain-related learning
Appetitive and aversive conditioning are both fundamental to adaptive behaviour, yet there remains limited understanding of how they differ on the behavioural and neural level. We investigated the two processes during acquisition and extinction using functional magnetic resonance imaging and behavioural measures. In a within-subject differential conditioning paradigm (preregistration DRKS00027448)...
Li, J.
•
Schmidt, K.
•
Busch, L.
•
Forkmann, K.
...•
Bingel, U.
biorxiv
Thu Apr 03 2025
Estimating Brain Similarity Networks with Diffusion MRI
Structural similarity has emerged as a promising tool in mapping the network organization of an individual, living human brain. Here, we propose diffusion similarity networks (DSNs), which employ rotationally invariant spherical harmonic features derived from diffusion magnetic resonance imaging (dMRI), to map gray matter structural organization. Compared to prior approaches, DSNs showed clearer l...
Sadikov, A.
•
Choi, H.
•
Cai, L. T.
•
Mukherjee, P.
biorxiv
Thu Apr 03 2025
Synaptic Connectivity of Sensorimotor Circuits for Vocal Imitation in the Songbird
Sensorimotor computations for learning and behavior rely on precise patterns of synaptic connectivity. Yet, we typically lack the synaptic wiring diagrams for long-range connections between sensory and motor circuits in the brain. Here we provide the synaptic wiring diagram for sensorimotor circuits involved in learning and production of male zebra finch song, a natural and ethologically relevant ...
Trusel, M.
•
Zhao, Z.
•
Alam, D.
•
Marks, E.
...•
Roberts, T. F.
biorxiv
Thu Apr 03 2025
Inferring global exponents in subsampled neural systems
In systems displaying an activity charaterized by avalanches, critical exponents may give informations on the mechanisms underlying the observed behaviour or on the topology of the connections. However, when only a small fraction of the units composing the system are observed and sampled, the measured exponents may differ significantly from the true ones. In this study, using Branching Process and...
Conte, D.
•
de Candia, A.
biorxiv
Thu Apr 03 2025
Sensory responsivity and its connection to sympathetic activation and deactivation: implications for stress and learning
This study introduces sensory responsivity (SR), which describes individual differences in sensory stimuli response strength and is hypothesised to affect stress responses in students and, in turn, their learning. To investigate this, a scale to assess SR was developed and linked to physiological responses. To this end, electrodermal activity (EDA) and sensory gating data was collected from a labo...
Flo, E. E.
biorxiv
Thu Apr 03 2025
The Organization of Serotonergic Fibers in the Pacific Angelshark Brain: Neuroanatomical and Supercomputing Analyses
Serotonergic axons (fibers) are a universal feature of all vertebrate brains. They form meshworks, typically quantified with regional density measurements, and appear to support neuroplasticity. The self-organization of this system remains poorly understood, partly because of the strong stochasticity of individual fiber trajectories. In an extension to our previous analyses of the mouse brain, ser...
Janusonis, S.
•
Metzler, R.
•
Vojta, T.
biorxiv
Thu Apr 03 2025
The extended language network: Language selective brain areas whose contributions to language remain to be discovered
Although language neuroscience has largely focused on core left frontal and temporal brain areas and their right-hemisphere homotopes, numerous other areas - cortical, subcortical, and cerebellar - have been implicated in linguistic processing. However, these areas\' contributions to language remain unclear given that the evidence for their recruitment comes from diverse paradigms, many of which c...
Wolna, A.
•
Wright, A.
•
Lipkin, B.
•
Fedorenko, E.