Biomaterial Database

Mechanism of voltage sensing in Ca2+- and voltage-activated K+ (BK) channels. 2022

Willy Carrasquel-Ursulaez, and Ignacio Segura, and Ignacio Díaz-Franulic, and Felipe Echeverría, and Yenisleidy Lorenzo-Ceballos, and Nicolás Espinoza, and Maximiliano Rojas, and Jose Antonio Garate, and Eduardo Perozo, and Osvaldo Alvarez, and Fernando D Gonzalez-Nilo, and Ramón Latorre

Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2340000, Chile.

In neurosecretion, allosteric communication between voltage sensors and Ca2+ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D001120	Arginine	An essential amino acid that is physiologically active in the L-form.	Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate
D015640	Ion Channel Gating	The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.	Gating, Ion Channel,Gatings, Ion Channel,Ion Channel Gatings
D051036	Large-Conductance Calcium-Activated Potassium Channels	A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.	BK Channel,Big K Channel,Large-Conductance Calcium-Activated Potassium Channel,Maxi K Channel,Maxi-K Channel,MaxiK Channel,BK Channels,Big K Channels,Maxi-K Channels,MaxiK Channels,Channel, BK,Channel, Big K,Channel, Maxi K,Channel, Maxi-K,Channel, MaxiK,K Channel, Big,K Channel, Maxi,Large Conductance Calcium Activated Potassium Channel,Large Conductance Calcium Activated Potassium Channels,Maxi K Channels
D056004	Molecular Dynamics Simulation	A computer simulation developed to study the motion of molecules over a period of time.	Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics