BKca1CHANNEL REGULATION BY PKG IN VASCULAR SMOOTH MUSCLE

PKG 对血管平滑肌的 BKca1 通道调节

• 批准号: 7673410
• 负责人: DANIEL E COX
• 金额: $ 31.37万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7673410
• 关键词: Address; Arteries; Arts; Attenuated; Binding; Biochemical; Blood Vessels; Calcium; Cardiovascular Diseases; Cardiovascular system; Cells; Characteristics; Collaborations; Contracts; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Dependence; Development; Disease; Elevation; Event; Genetically Engineered Mouse; Hypertension; Image; Imaging Techniques; Ion Channel; Kinetics; Laboratories; Leucine Zippers; Life; Literature; Localized; Mediating; Mediator of activation protein; Molecular; Monitor; Mus; Muscle Contraction; Muscle relaxation phase; Mutation; Nature; Nitric Oxide; Phenotype; Phosphoric Monoester Hydrolases; Phosphorylation; Physiological Processes; Physiology; Play; Protein Kinase C; Protein Kinase Interaction; Proteins; Regulation; Relaxation; Reticulum; Role; Signal Pathway; Simulate; Smooth Muscle; Smooth Muscle Myocytes; Source; Techniques; Testing; Thinking; Transgenic Organisms; Vascular Smooth Muscle; Vasodilator Agents; Work; cerebral artery; channel blockers; citrate carrier; design; drug development; in vivo; large-conductance calcium-activated potassium channels; mouse model; mutant; novel; patch clamp; response; vasomotion; voltage

Large-conductance Ca2+-activated K+ (BK[Ca]) channels play a critical role in the regulation ofl vascular tone, and they are thought to be important mediators of the vasodilatory effects of endothelial derived NO and exogenous vasodilators that activate the cGMP-dependent protein kinase (PKG). Here we propose to address questions that relate to the BK[Ca] channel's activation by PKG in vascular smooth muscle. In Aim 1 we will address questions having to do with the biochemical mechanism by which the BK[Ca] channel is activated by PKG. Does PKG stably associate with channel? Is a phosphatase required for PKG-mediated BK[Ca] -channel activation? Is the BK[Ca] channel's smooth muscle-specific beta1 subunit required? And does protein kinase C modulate the effect of PKG on the BK channel? In Aim 2 we will focus on the nature of PKG's effect, examining particularly its Ca2+ -dependence and its effect on the response of the channel to a Ca 2+ spark. And in Aim 3 we will examine whether PKGlalpha's leucine zipper domain is required for PKG-mediated modulation of Ca 2+ sparking and BK[Ca] channel opening in vivo. Results from the proposed work are expected to advance our understanding of the regulation of a key ion channel that regulates vasomotion, and they may suggest new strategies for the development of drugs to treat hypertension and ischemic cardiovascular diseases.

大电导Ca2+激活的K+ (BK[Ca])通道在l的调控中起关键作用