{"id":4114,"date":"2024-10-01T07:00:43","date_gmt":"2024-10-01T07:00:43","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/poster\/electrophysiological-characterisation-of-functional-and-pharmacological-effects-of-%ce%b2-subunit-expression-on-bk-channel-activity\/"},"modified":"2026-01-22T14:56:15","modified_gmt":"2026-01-22T14:56:15","slug":"electrophysiological-characterisation-of-functional-and-pharmacological-effects-of-%ce%b2-subunit-expression-on-bk-channel-activity","status":"publish","type":"poster","link":"https:\/\/www.sygnaturediscovery.com\/fr\/poster\/electrophysiological-characterisation-of-functional-and-pharmacological-effects-of-%ce%b2-subunit-expression-on-bk-channel-activity\/","title":{"rendered":"Electrophysiological characterisation of functional and pharmacological effects of \u03b2 subunit expression on BK channel activity."},"content":{"rendered":"

BK channels are large conductance potassium channels which are expressed in a broad range of excitable as well as non-excitable cell types and are activated by elevations in cytosolic Ca2+<\/sup> concentration and membrane depolarization. It is thought that these channels have discrete physiological roles that are adapted to the specific cell type requirements and depend on cell-specific membrane potentials and cytosolic Ca2+<\/sup> concentrations. To accomplish such a broad diversity in physiological roles, BK channels consist of a pore forming \u03b1 subunit and employ auxiliary subunits (\u03b21-4<\/sub> or \u03b31-4<\/sub>) to enable the variety of functional roles.<\/p>\n

Modulation of BK channels has been suggested as a therapeutic strategy for a number of disorders including epilepsy, Alzheimer\u2019s disease and schizophrenia. However, the widespread expression of BK channels and their participation in a variety of essential physiological processes mean that any therapeutic strategy aimed at one particular cell type, tissue, or organ system risks impacting other cells and tissues unrelated to the pathology, perhaps with highly undesirable consequences. To reduce this risk, specific targeting of particular BK \/ auxiliary subunit combinations may prove beneficial, with the aim to selectively modulate specific BK subsets and reduce unwanted side-effects.<\/p>\n

To investigate the functional and pharmacological effect of different \u03b2 subunits on BK activity, recombinant HEK cell lines expressing BK \u03b1, \u03b1\u03b21, \u03b1\u03b22 and \u03b1\u03b24 combinations were developed and characterized using a high throughput automated patch clamp platform. Simultaneous assessment of multiple BK subtypes allowed for rapid optimization and characterization. Firstly, the current-voltage (IV) relationship was assessed in the presence of various free internal Ca2+<\/sup> concentrations (0, 1, 3, and 10 \u00b5M), with the \u03b2 containing BK channels displaying increased sensitivity to intracellular Ca2+<\/sup> in line with literature values. The general BK activator NS1619 was assessed with calculated EC50 <\/sub>values in the range of 10-20 \u00b5M, while the activator Arachidonic Acid was selective for \u03b1\u03b21 over \u03b1 only expressing cells.<\/p>\n

In inhibitor mode, the calculated IC50<\/sub> of the BK antagonist Paxilline was in the range of 30-130 nM depending on the specific BK \u03b1\u03b2 subunit complex, while Iberiotoxin was selective for BK\u03b1 alone, in line with previous studies.<\/p>\n

The characterization performed here enables the identification of pharmacological compounds targeting particular BK \u03b1\u03b2 subunit combinations and provides opportunities to selectively target BK channels involved in particular physiological disorders.<\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":2838,"template":"","category":[681,709,707,746,780,687],"class_list":["post-4114","poster","type-poster","status-publish","has-post-thumbnail","hentry","category-bioscience","category-cell-based-assays","category-electrophysiology","category-ion-channels","category-potassium-channels","category-target-classes"],"acf":[],"yoast_head":"\nElectrophysiological characterisation of functional and pharmacological effects of \u03b2 subunit expression on BK channel activity. - Sygnature<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/poster\/electrophysiological-characterisation-of-functional-and-pharmacological-effects-of-%ce%b2-subunit-expression-on-bk-channel-activity\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Electrophysiological characterisation of functional and pharmacological effects of \u03b2 subunit expression on BK channel activity. - 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