K ions exert a structural effect that brings stability to K selective pores. Thus, upon bathing Shab channels in 0 K solutions the ion conductance, G, irreversibly collapses. Related to this, studies with isolated KcsA channels have suggested that there is a transition [K] around which the pore takes one of two conformations, either the low (non-conducting) or high K (conducting) crystal structures. We examined this premise by looking at the K-dependency of G stability of Shab channels within the cell membrane environment. We found that: K effect on G stability is highly asymmetrical, and that as internal K is replaced by Na G drops in a way that suggests a transition internal [K]. Additionally, we found that external permeant ions inhibit G drop with a potency that differs from the global selectivity-sequence of K pores; the non-permeant TEA inhibited G drop in a K-dependent manner. Upon lowering internal [K] we observed an influx of Na at negative potentials. Na influx was halted by physiological external [K], which also restored G stability. Hyperpolarized potentials afforded G stability but, as expected, do not restore G selectivity. For completeness, Na interaction with Shab was also assessed at depolarized potentials by looking at Na block followed by permeation (pore unblock) at positive potentials, in solutions approaching the 0 K limit. The stabilizing effect of negative potentials along with the non-parallel variation of Na permeability and conductance-stability herein reported, show that pore stability and selectivity, although related, are not strictly coupled.
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http://dx.doi.org/10.1080/19336950.2021.1993037 | DOI Listing |
J Biol Chem
January 2025
Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA; Molecular, Cellular & Integrated Neurosciences, Colorado State University, Fort Collins, CO 80523, USA; Cell & Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address:
The Shab family voltage-gated K channels (i.e., Kv2.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Epilepsy Center, Children's Hospital Affiliated to Shandong University, Jinan, China.
Rationale: Developmental and epileptic encephalopathy (DEE) defines a group of severe and heterogeneous neurodevelopmental disorders. The voltage-gated potassium channel subfamily 2 voltage-gated potassium channel α subunit encoded by the KCNB1 gene is essential for neuronal excitability. Previous studies have shown that KCNB1 variants can cause DEE.
View Article and Find Full Text PDFCommun Biol
December 2024
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
Integrin_K Channel_Complexes (IKCs), are implicated in neurodevelopment and cause developmental and epileptic encephalopathy (DEE) through mechanisms that were poorly understood. Here, we investigate the function of neocortical IKCs formed by voltage-gated potassium (Kv) channels Kcnb1 and α5β5 integrin dimers in wild-type (WT) and homozygous knock-in (KI) Kcnb1 mouse model of DEE. Kcnb1 mice suffer from severe cognitive deficit and compulsive behavior.
View Article and Find Full Text PDFClin Chim Acta
January 2025
Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun 130021, China. Electronic address:
FASEB J
October 2024
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, USA.
The neurons of the melanocortin system regulate feeding and energy homeostasis through a combination of electrical and endocrine mechanisms. However, the molecular basis for this functional heterogeneity is poorly understood. Here, a voltage-gated potassium (Kv) channel named KCNB1 (alias Kv2.
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