Excitatory cholinergic responses in mouse primary bronchial smooth muscle require both Ca entry via l-type Ca channels and store operated Ca entry via Orai channels.

Malfunctions in airway smooth muscle Ca-signalling leads to airway hyperresponsiveness in asthma and chronic obstructive pulmonary disease. Ca-release from intracellular stores is important in mediating agonist-induced contractions, but the role of influx via l-type Ca channels is controversial. We re-examined roles of the sarcoplasmic reticulum Ca store, refilling of this store via store-operated Ca entry (SOCE) and l-type Ca channel pathways on carbachol (CCh, 0.

Oxidation modulates LINGO2-induced inactivation of large conductance, Ca-activated potassium channels.

Ca and voltage-activated K (BK) channels are ubiquitous ion channels that can be modulated by accessory proteins, including β, γ, and LINGO1 BK subunits. In this study, we utilized a combination of site-directed mutagenesis, patch clamp electrophysiology, and molecular modeling to investigate if the biophysical properties of BK currents were affected by coexpression of LINGO2 and to examine how they are regulated by oxidation. We demonstrate that LINGO2 is a regulator of BK channels, since its coexpression with BK channels yields rapid inactivating currents, the activation of which is shifted ∼-30 mV compared to that of BKα currents.

Calcium-Activated K Channels (K) and Therapeutic Implications.

Potassium channels are the most diverse and ubiquitous family of ion channels found in cells. The Ca and voltage gated members form a subfamily that play a variety of roles in both excitable and non-excitable cells and are further classified on the basis of their single channel conductance to form the small conductance (SK), intermediate conductance (IK) and big conductance (BK) K channels.In this chapter, we will focus on the mechanisms underlying the gating of BK channels, whose function is modified in different tissues by different splice variants as well as the expanding array of regulatory accessory subunits including β, γ and LINGO subunits.

LINGO1 is a regulatory subunit of large conductance, Ca-activated potassium channels.

LINGO1 is a transmembrane protein that is up-regulated in the cerebellum of patients with Parkinson's disease (PD) and Essential Tremor (ET). Patients with additional copies of the LINGO1 gene also present with tremor. Pharmacological or genetic ablation of large conductance Ca-activated K (BK) channels also result in tremor and motor disorders.

Vasodilation of rat skeletal muscle arteries by the novel BK channel opener GoSlo is mediated by the simultaneous activation of BK and K 7 channels.

Background And Purpose: BK channels play important roles in various physiological and pathophysiological processes and thus have been the target of several drug development programmes focused on creating new efficacious BK channel openers, such as the GoSlo-SR compounds. However, the effect of GoSlo-SR compounds on vascular smooth muscle has not been studied. Therefore, we tested the hypothesis that GoSlo-SR compounds dilate arteries exclusively by activating BK channels.