Atomistic mechanisms of the regulation of small-conductance Ca-activated K channel (SK2) by PIP2.

Small-conductance Ca-activated K channels (SK, K2) are gated solely by intracellular microdomain Ca. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca sensor to gate the channels.

The Piezo channel is a mechano-sensitive complex component in the mammalian inner ear hair cell.

The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known.

Adenylyl cyclase isoform 1 contributes to sinoatrial node automaticity via functional microdomains.

Sinoatrial node (SAN) cells are the heart's primary pacemaker. Their activity is tightly regulated by β-adrenergic receptor (β-AR) signaling. Adenylyl cyclase (AC) is a key enzyme in the β-AR pathway that catalyzes the production of cAMP.

Different arrhythmia-associated calmodulin mutations have distinct effects on cardiac SK channel regulation.

Calmodulin (CaM) plays a critical role in intracellular signaling and regulation of Ca2+-dependent proteins and ion channels. Mutations in CaM cause life-threatening cardiac arrhythmias. Among the known CaM targets, small-conductance Ca2+-activated K+ (SK) channels are unique, since they are gated solely by beat-to-beat changes in intracellular Ca2+.

Gating Properties of Mutant Sodium Channels and Responses to Sodium Current Inhibitors Predict Mexiletine-Sensitive Mutations of Long QT Syndrome 3.

Background: Long QT syndrome 3 (LQT3) is caused by mutations. Late sodium current (late ) inhibitors are current-specific to treat patients with LQT3, but the mechanisms underlying mexiletine (MEX) -sensitive (N1325S and R1623Q) and -insensitive (M1652R) mutations remains to be elucidated.

Methods: LQT3 patients with causative mutations were treated with oral MEX following i.

A double-stranded RNA platform is required for the interaction between a host restriction factor and the NS1 protein of influenza A virus.

Influenza A viruses cause widespread human respiratory disease. The viral multifunctional NS1 protein inhibits host antiviral responses. This inhibition results from the binding of specific cellular antiviral proteins at various positions on the NS1 protein.

Mechanisms of Calmodulin Regulation of Different Isoforms of Kv7.4 K+ Channels.

Calmodulin (CaM), a Ca(2+)-sensing protein, is constitutively bound to IQ domains of the C termini of human Kv7 (hKv7, KCNQ) channels to mediate Ca(2+)-dependent reduction of Kv7 currents. However, the mechanism remains unclear. We report that CaM binds to two isoforms of the hKv7.

Regulation of gene transcription by voltage-gated L-type calcium channel, Cav1.3.

Cav1.3 L-type Ca(2+) channel is known to be highly expressed in neurons and neuroendocrine cells. However, we have previously demonstrated that the Cav1.

Functional interaction with filamin A and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca2+-activated K+ (SK2) channel.

For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca(2+)-activated K(+) channels (KCa2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile.

Adenylyl cyclase subtype-specific compartmentalization: differential regulation of L-type Ca2+ current in ventricular myocytes.

Rationale: Adenylyl cyclase (AC) represents one of the principal molecules in the β-adrenergic receptor signaling pathway, responsible for the conversion of ATP to the second messenger, cAMP. AC types 5 (ACV) and 6 (ACVI) are the 2 main isoforms in the heart. Although highly homologous in sequence, these 2 proteins play different roles during the development of heart failure.