Publications by authors named "Willy Carrasquel-Ursulaez"

In neurosecretion, allosteric communication between voltage sensors and Ca 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.

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Synthetic ion channels based on benzo(crown-ether) compounds have been previously reported to function as ion-selective channels in planar lipid bilayers, with hydrogen bonding networks implicated in the formation of self-aggregated complexes. Herein, we report the synthesis and characterization of two new families of benzo(crown-ether) compounds, termed monoacylated and monoalkylated benzo(crown-ethers) (MABCE), both of which lack hydrogen bond donors. Depending on the length of alkyl chain substituent and the size of macrocycle, MABCE compounds inhibit bacterial growth and transport ions across biological membranes.

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Despite a growing number of ion channel genes implicated in hereditary ataxia, it remains unclear how ion channel mutations lead to loss-of-function or death of cerebellar neurons. Mutations in the gene , encoding the α-subunit of the BK channel have emerged as responsible for a variety of neurological phenotypes. We describe a mutation (BK) in , in a child with congenital and progressive cerebellar ataxia with cognitive impairment.

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The cytotoxicity of dialkylated lariat ethers has been previously attributed to their ionophoric properties. Herein, we provide evidence that these effects are due to loss of membrane integrity rather than ion transport, a finding with important implications for the future design of synthetic ionophores.

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Allosteric interactions between the voltage-sensing domain (VSD), the Ca-binding sites, and the pore domain govern the mammalian Ca- and voltage-activated K (BK) channel opening. However, the functional relevance of the crosstalk between the Ca- and voltage-sensing mechanisms on BK channel gating is still debated. We examined the energetic interaction between Ca binding and VSD activation by investigating the effects of internal Ca on BK channel gating currents.

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The accessory β1 subunit modulates the Ca- and voltage-activated K (BK) channel gating properties mainly by increasing its apparent Ca sensitivity. β1 plays an important role in the modulation of arterial tone and blood pressure by vascular smooth muscle cells (SMCs). 17β-estradiol (E2) increases the BK channel open probability (P) in SMCs, through a β1 subunit-dependent modulatory effect.

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Two families of accessory proteins, β and γ, modulate BK channel gating and pharmacology. Notably, in the absence of internal Ca, the γ1 subunit promotes a large shift of the BK conductance-voltage curve to more negative potentials. However, very little is known about how α- and γ1 subunits interact.

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Large-conductance Ca- and voltage-activated K (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies.

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Mammals maintain homeostatic control of their body temperature. Therefore, these organisms are expected to have adaptations that confer the ability to detect and react to both self and ambient temperature. Temperature-activated ion channels have been discovered to be the primary molecular determinants of thermosensation.

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Large-conductance Ca(2+)- and voltage-activated K(+) channel (BK) open probability is enhanced by depolarization, increasing Ca(2+) concentration, or both. These stimuli activate modular voltage and Ca(2+) sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca(2+), profoundly hinders channel opening while showing only minor effects on the voltage sensor active-resting equilibrium.

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Calcium and voltage-activated potassium (BK) channels are key actors in cell physiology, both in neuronal and non-neuronal cells and tissues. Through negative feedback between intracellular Ca (2+) and membrane voltage, BK channels provide a damping mechanism for excitatory signals. Molecular modulation of these channels by alternative splicing, auxiliary subunits and post-translational modifications showed that these channels are subjected to many mechanisms that add diversity to the BK channel α subunit gene.

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