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Ryanodine receptors as pharmacological targets for heart disease

Acta Pharmacologica Sinica 2007年第7期28卷 937-944页

作者： Marco SANTONASTAS Xander H T WEHRENS Departments of Molecular Physiology and Biophysics Departments of Molecular Physiology and Biophysics and Medieine(Cardiology) Baylor College of MedicineHoustonTexas 77030USA

calcium release from intracellular stores plays an important role in the regulationof muscle contraction and electrical signals that determine the heart rhythm.Theryanodine receptor （RyR） is the major calcium (Ca2+) release channel required forexcitation-contraction coupling in the heart.Recent studies have demonstratedthat RyR are macromolecular complexes comprising of 4 pore-forming channelsubunits,each of which is associated with regulatory subunits.Clinical andexperimental studies over the past 5 years have provided compelling evidencethat intracellular Ca2+release channels play a pivotal role in the development ofcardiac arrhythmias and heart failure.Changes in the channel regulation andsubunit composition are believed to cause diastolic calcium leakage from thesarcoplasmic reticulum,which could trigger arrhythmias and weaken cardiaccontractility.Therefore,cardiac RyR have emerged as potential therapeutic tar-gets for the treatment of heart disease.Consequently,there is a strong desire toidentify and/or develop novel pharmacological agents that may target these Ca2+signaling pathways.Pharmacological agents known to modulate RyR in the heart,and their potential application towards the treatment of heart disease are dis-cussed in this review.

关键词： arrhythmias calcium release channel heart failure pharmacology ryanodine receptor

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

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Journal of Nanjing Medical University 2002年第2期16卷 75-79页

作者：刘乃丰张寄南耿茜杨笛董莉马文珠 Division of Cardiology Zhongda Hospital Southeast University Nanjing 210009 Research Institute of Cardiovascular Diseases NJMU Nanjing 210029 P. R. China

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.

关键词： calcium release channel signal transduction inositol 1,4,5 trisphosphate receptor spontaneous hypertension rat vascular smooth muscle cultured cells polymers chain reaction

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