TRP channels and kidney disease: lessons from polycystic kidney disease

2007 ◽  
Vol 35 (1) ◽  
pp. 124-128 ◽  
Author(s):  
S. Qamar ◽  
M. Vadivelu ◽  
R. Sandford
Keyword(s):  
Kidney Disease ◽  
Intracellular Calcium ◽  
Polycystic Kidney Disease ◽  
Primary Cilium ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Polycystic Kidney ◽  
Pkd2 Gene ◽  
Transient Receptor

Important insights in to the function of members of the TRP (transient receptor potential) channel superfamily have been gained from the identification of disease-related mutations. In particular the identification of mutations in the PKD2 gene in autosomal dominant polycystic kidney disease has revealed a link between TRP channel function, mechanosensation and the role of the primary cilium in renal cyst formation. The PKD2 gene encodes TRPP2 (transient receptor potential polycystin 2) that has significant homology to voltage-activated calcium and sodium TRP channels. It interacts with polycystin-1 to form a large membrane-associated complex that is localized to the renal primary cilium. Functional characterization of this polycystin complex reveals that it can respond to mechanical stimuli such as flow, resulting in influx of extracellular calcium and release of calcium from intracellular stores. TRPP2 is expressed in the endoplasmic reticulum/sarcoplasmic reticulum where it also regulates intracellular calcium signalling. Therefore TRPP2 modulates many cellular processes via intracellular calcium-dependent signalling pathways.

scholarly journals A microbial TRP-like polycystic-kidney-disease-related ion channel gene

2005 ◽  
Vol 387 (1) ◽  
pp. 211-219 ◽  
Author(s):  
Christopher P. PALMER ◽  
Ebru AYDAR ◽  
Mustafa B. A. DJAMGOZ
Keyword(s):  
Cell Wall ◽  
Kidney Disease ◽  
Ion Channel ◽  
Polycystic Kidney Disease ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cell Wall Synthesis ◽  
Polycystic Kidney ◽  
Channel Gene ◽  
Ion Channel Gene

Ion channel genes have been discovered in many microbial organisms. We have investigated a microbial TRP (transient receptor potential) ion channel gene which has most similarity to polycystic-kidney-disease-related ion channel genes. We have shown that this gene (pkd2) is essential for cellular viability, and is involved in cell growth and cell wall synthesis. Expression of this gene increases following damage to the cell wall. This fission yeast pkd2 gene, orthologues of which are found in all eukaryotic cells, appears to be a key signalling component in the regulation of cell shape and cell wall synthesis in yeast through an interaction with a Rho1-GTPase. A model for the mode of action of this Schizosaccharomyces pombe protein in a Ca2+ signalling pathway is hypothesized.

scholarly journals Deciphering physiological role of the mechanosensitive TRPV4 channel in the distal nephron

2015 ◽  
Vol 308 (4) ◽  
pp. F275-F286 ◽  
Author(s):  
M. Mamenko ◽  
O. Zaika ◽  
N. Boukelmoune ◽  
R. G. O'Neil ◽  
O. Pochynyuk
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Renal Tubule ◽  
Trp Channels ◽  
Current Evidence ◽  
Distal Nephron ◽  
Polycystic Kidney ◽  
Intracellular Ca

Long-standing experimental evidence suggests that epithelial cells in the renal tubule are able to sense osmotic and pressure gradients caused by alterations in ultrafiltrate flow by elevating intracellular Ca2+ concentration. These responses are viewed as critical regulators of a variety of processes ranging from transport of water and solutes to cellular growth and differentiation. A loss in the ability to sense mechanical stimuli has been implicated in numerous pathologies associated with systemic imbalance of electrolytes and to the development of polycystic kidney disease. The molecular mechanisms conferring mechanosensitive properties to epithelial tubular cells involve activation of transient receptor potential (TRP) channels, such as TRPV4, allowing direct Ca2+ influx to increase intracellular Ca2+ concentration. In this review, we critically analyze the current evidence about signaling determinants of TRPV4 activation by luminal flow in the distal nephron and discuss how dysfunction of this mechanism contributes to the progression of polycystic kidney disease. We also review the physiological relevance of TRPV4-based mechanosensitivity in controlling flow-dependent K+ secretion in the distal renal tubule.

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

2011 ◽  
Vol 110 (3) ◽  
pp. 789-798 ◽  
Author(s):  
Kaori Ono ◽  
Masako Tsukamoto-Yasui ◽  
Yoshiko Hara-Kimura ◽  
Naohiko Inoue ◽  
Yoshihito Nogusa ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Low Frequency ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Intragastric Administration ◽  
Brown Adipose ◽  
Reflex Arc ◽  
Transient Receptor

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

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