Expression of Inositol 1,4,5-trisphosphate Receptor mRNA in Myocardium of Spontaneous Hypertension Rats and Cultured Vascular Smooth Muscle Cells of Rats

Objective\ To investigate expression of inositol 1,4,5 trisphosphate receptor (IP\-3R) mRNA on sacroplasmic reticular in myocardium of spontaneous hypertension rats (SHRs) and cultured vascular smooth muscle cells (VSMC) of rats and effects of perindopril and urapidil on them. Methods\ SHRs were orally given perindopril (1.0 mg·kg\+\{ 1\}·d\+\{ 1\}) or urapidil (15 mg·kg\+\{ 1\}·d\+\{ 1\}) for 24 weeks, respectively. Expression of IP\-3R mRNA was examined by semi quantitative reverse transcription polymers chain reaction (RT PCR) using three oligonuclotide primers for each subtype of IP\-3R with β actin as internal label. Results\ All subtypes of IP\-3R were expressed in myocardium of SHR, WKY and cultured VSMC. Expression of IP\-3R mRNA in left ventricle of SHR was markedly enhanced. Urapidil could down regulate expression of IP\-3R Ⅰand IP\-3R Ⅲ, perindopril slightly increased expression of IP\-3R Ⅱ and decreased expression of IP\-3R Ⅰand IP\-3R Ⅲ in myocardium of SHR. Conclusion\ Our results suggest that expression of IP\-3R mRNA in cardiovascular system could be regulated by urapidil and perindopril.

The effects of local anesthetics on intracellular Ca2+ release from ryanod ine-sensitive Ca2+ stores in gerbil hippocampal neurons

OBJECTIVE: To examine the effects of procaine and lidocaine on intracellular Ca(2+) release from sarcoplasmic reticulum ryanodine-sensitive Ca(2+) stores. METHODS: The experiment was performed on hippocampal slices from 60-80 g male Mongolian gerbils. Levels of intracellular Ca(2+) concentration in the slices were measured by microfluorometry. The slices were perfused with 50 mmol/L KCl containing medium for 30 seconds. Then, the medium was switched to physiological medium. After 5 min of incubation, the slice was perfused with 20 mmol/L caffeine containing physiology medium for 2 min. Following incubation, the slice was superfused with physiological medium until the end of the experiment. The effects of procaine and lidocanin (100 micro mol/L) on caffeine-evoked Ca(2+) release were evaluated by adding them to the medium after high K(+) medium perfusion. RESULTS: Caffeine induced a marked increase in intracellular Ca(2+) concentration which was then decreased 12% upon the addition of procaine (P

The structural biology of ryanodine receptors

Ryanodine receptors are ion channels that allow for the release of Ca2+ from the endoplasmic or sarcoplasmic reticulum.They are expressed in many different cell types but are best known for their predominance in skeletal and cardiac myocytes,where they are directly involved in excitation-contraction coupling.With molecular weights exceeding 2 MDa,Ryanodine Receptors are the largest ion channels known to date and present major challenges for structural biology.Since their discovery in the 1980s,significant progress has been made in understanding their behaviour through multiple structural methods.Cryo-electron microscopy reconstructions of intact channels depict a mushroom-shaped structure with a large cytoplasmic region that pre-sents many binding sites for regulatory molecules.This region undergoes significant motions during opening and closing of the channel,demonstrating that the Ryanodine Receptor is a bona fide allosteric protein.High-resolution structures through X-ray crystallography and NMR currently cover～11% of the entire protein.The combination of high-and low-resolution methods allows us to build pseudo-atomic models.Here we present an overview of the electron microscopy,NMR,and crystallographic analyses of this membrane protein giant.