Ca signaling of pancreatic acinar cells in malignant hyperthermia susceptibility.

Background: Malignant hyperthermia susceptibility (MHS) and acute pancreatitis (AP) share a common cellular pathomechanism that is Ca-overload of the muscle fiber and the pancreatic acinar cell (PAC). In the muscle, gain-of-function mutations of the ryanodine receptor (RyR1) make the Ca-release mechanism hypersensitive to certain ligands, including Ca, volatile anaesthetics and succinylcholine, creating a medical emergency when the patient is exposed to these drugs. As RyR1 was shown to contribute to Ca-overload in PAC, we presumed that pancreata of MHS individuals are more prone to AP.

The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension.

Background And Purpose: Pulmonary arterial hypertension (PAH) is a progressive disease in which chronic membrane potential (E) depolarisation of the pulmonary arterial smooth muscle cells (PASMCs) causes calcium overload, a key pathological alteration. Under resting conditions, the negative E is mainly set by two pore domain potassium (K) channels, of which the TASK-1 has been extensively investigated.

Experimental Approach: Ion channel currents and membrane potential of primary cultured human(h) PASMCs were measured using the voltage- and current clamp methods.

Function of a mutant ryanodine receptor (T4709M) linked to congenital myopathy.

Physiological muscle contraction requires an intact ligand gating mechanism of the ryanodine receptor 1 (RyR1), the Ca-release channel of the sarcoplasmic reticulum. Some mutations impair the gating and thus cause muscle disease. The RyR1 mutation T4706M is linked to a myopathy characterized by muscle weakness.

Eu detects two functionally distinct luminal Ca binding sites in ryanodine receptors.

Ryanodine receptors (RyRs) are Ca release channels, gated by Ca in the cytosol and the sarcoplasmic reticulum lumen. Their regulation is impaired in certain cardiac and muscle diseases. Although a lot of data is available on the luminal Ca regulation of RyR, its interpretation is complicated by the possibility that the divalent ions used to probe the luminal binding sites may contaminate the cytoplasmic sites by crossing the channel pore.

Functional characterization of the transient receptor potential melastatin 2 (TRPM2) cation channel from Nematostella vectensis reconstituted into lipid bilayer.

Transient receptor potential melastatin 2 (TRPM2) cation channel activity is required for insulin secretion, immune cell activation and body heat control. Channel activation upon oxidative stress is involved in the pathology of stroke and neurodegenerative disorders. Cytosolic Ca, ADP-ribose (ADPR) and phosphatidylinositol-4,5-bisphosphate (PIP) are the obligate activators of the channel.