Respir Res
July 2024
Background: Cystic Fibrosis causing mutations in the gene , reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2017
Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, leading to defective apical chloride transport. Patients also experience overactivation of inflammatory processes, including increased calcium signaling. Many investigations have described indirect effects of calcium signaling on CFTR or other calcium-activated chloride channels; here, we investigate the direct response of CFTR to calmodulin-mediated calcium signaling.
View Article and Find Full Text PDFBackground: Electrocardiographic signature of escape capture bigeminy that spans generations and clusters in a family has not been linked to a sodium channel voltage sensor mutation.
Objective: To characterize the clinical and biophysical consequences of the R222Q mutation in the voltage sensor of cardiac sodium channels.
Methods: Comprehensive clinical assessment, invasive electrophysiologic study, genetic analysis, and patch-clamp studies were undertaken.
HCN channels are thought to be structurally similar to Kv channels, but show much lower selectivity for K+. The approximately 3.3 A selectivity filter of K+ channels is formed by the pore-lining sequence XT(V/I)GYG, with X usually T, and is held stable by key residues in the P-loop.
View Article and Find Full Text PDFThyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH.
View Article and Find Full Text PDFIon channel conductance can be influenced by electrostatic effects originating from fixed "surface" charges that are remote from the selectivity filter. To explore whether surface charges contribute to the conductance properties of Kir2.1 channels, unitary conductance was measured in cell-attached recordings of Chinese hamster ovary (CHO) cells transfected with Kir2.
View Article and Find Full Text PDFCardiac inward rectifier K+ currents (IK1) play an important role in maintaining resting membrane potential and contribute to late phase repolarization. Members of the Kir2.x channel family appear to encode for IK1.
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