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.
View Article and Find Full Text PDFBackground 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.
Fine control over chloride homeostasis in the lung is required to maintain membrane excitability, transepithelial transport as well as intra- and extracellular ion and water homeostasis. Over the last decades, a growing number of chloride channels and transporters have been identified in the cells of the pulmonary vasculature and the respiratory tract. The importance of these proteins is underpinned by the fact that impairment of their physiological function is associated with functional dysregulation, structural remodeling, or hereditary diseases of the lung.
View Article and Find Full Text PDFThe transition from the fetal to the neonatal circulation includes dilatation of the pulmonary arteries (PA) and closure of the Ductus Arteriosus Botalli (DAB). The resting membrane potential and various potassium channel activities in smooth muscle cells (SMC) from fetal and neonatal PA and DAB obtained from the same species has not been systematically analyzed. The key issue addressed in this paper is how the resting membrane potential and the whole-cell potassium current (IK) change when PASMC or DABSMC are transitioned from hypoxia, reflecting the fetal state, to normoxia, reflecting the post-partal state.
View Article and Find Full Text PDFPotassium ion concentrations, controlled by ion pumps and potassium channels, predominantly govern a cell's membrane potential and the tone in the vessels. Calcium-activated potassium channels respond to two different stimuli-changes in voltage and/or changes in intracellular free calcium. Large conductance calcium-activated potassium (BKCa) channels assemble from pore forming and various modulatory and auxiliary subunits.
View Article and Find Full Text PDF