The role of HVA alpha1E Ca2+ channel subunit in micturition reflex pathways

HVA α1E Ca2 通道亚基在排尿反射通路中的作用

• 批准号: 8272661
• 负责人: Katarina Zvarova
• 金额: $ 13.63万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8272661
• 关键词: Address; Adenosine Triphosphate; Affect; Afferent Neurons; Animals; Applications Grants; Bladder; Bladder Urothelium; Calcium; Calcium Channel; Cell membrane; Cells; Data; Electrophysiology (science); Equilibrium; Functional disorder; Goals; In Vitro; Knowledge; Limb structure; Lower urinary tract; Mediating; Mediator of activation protein; Medical; Micturition Reflex; Molecular Biology; Muscle Contraction; Nerve; Neuronal Plasticity; Nitric Oxide; Pathway interactions; Pattern; Physiological; Play; Property; Rattus; Regulation; Research; Role; Sensory; Signal Transduction; Smooth Muscle; Spinal Cord; Spinal Ganglia; Techniques; Tissues; Urination; Urothelium; cellular imaging; in vivo; insight; neurotransmitter release; novel therapeutic intervention; public health relevance; voltage

DESCRIPTION (provided by applicant): Detrusor overactivity (DO) is a prevalent medical condition. Despite a growing body of research the pathomechanisms of this condition are still poorly understood and available therapy is ineffective. Calcium (Ca2+) entry through voltage dependent calcium channels (VDCCs) is an important factor for mediating urinary bladder smooth muscle (UBSM) contraction as well as for regulation of neurotransmitter release from nerve terminals. Disruption of this fine balance can result in a voiding dysfunction. This proposal focuses on VDCC CaV2.3 (R-type), its distribution and functional significance in rat urinary bladder and sensory micturition reflex pathways in healthy animals and animals with DO. The overall hypothesis for this grant proposal is that DO-induced neuroplasticity of micturition reflex pathways leads to changes in electrophysiological properties that affect the high voltage activated R-type Ca2+ channel subunit. These changes contribute to an alteration of the micturition reflex through affecting Ca2+ signal patterning in UBSM and bladder sensory neurons. Specific Aim 1: To determine distribution of (1E CaV2.3 (R-type) channel subunit in micturition reflex pathways and characterize changes in their expression associated with DO. Specific Aim 2: To elucidate UBSM and bladder sensory neuron Ca2+ signaling patterns mediated by R-type Ca2+ channels under physiological and pathological conditions. Specific Aim 3: To clarify the physiological significance of the R-type Ca2+ channel subunit in micturition. This proposal takes an integrative approach by applying molecular biology, cell imaging, electrophysiology and in vivo and in vitro functional techniques to identify the CaV2.3 channel in the lower urinary tract (LUT) and define its contribution to Ca2+ signaling under physiological and pathological conditions. To our knowledge, this is the first study addressing the specific role of R-type Ca2+ channel in the LUT. PUBLIC HEALTH RELEVANCE: Results from this study will significantly enhance current knowledge on the specific role of R-type Ca2+ channel in the lower urinary tract, and may provide insight into new therapeutic approaches for the treatment of bladder overactivity.

描述（由申请人提供）：

项目成果

Acute lower urinary tract dysfunction (LUTD) following traumatic brain injury (TBI) in rats.

大鼠脑外伤（TBI）后急性下尿路功能障碍（LUTD）。

• DOI: 10.1002/nau.22470
• 发表时间: 2014
• 期刊: Neurourology and urodynamics
• 影响因子: 2
• 作者: Moody,BenjaminJ;Liberman,Caleb;Zvara,Peter;Smith,PhillipP;Freeman,Kalev;Zvarova,Katarina
• 通讯作者: Zvarova,Katarina

Urinary bladder function in conscious rat pups: a developmental study.

清醒大鼠幼崽的膀胱功能：一项发育研究。

• DOI: 10.1152/ajprenal.00567.2011
• 发表时间: 2012
• 期刊: American journal of physiology. Renal physiology
• 作者: Zvarova,Katarina;Zvara,Peter
• 通讯作者: Zvara,Peter