Podocyte electrophysiology, in vivo and in vitro

Abstract

Podocytes are the most differentiated cell types in the glomerulus, which have been assumed to participate in the regulation of the ultrafiltration coefficient K(f). In podocytes in vivo and in vitro vasoactive agonists, such as angiotensin II and acetylcholine, increase the free cytosolic Ca(2+) concentration via a release of Ca(2+) from intracellular stores and an influx of Ca(2+) from the extracellular space. An increase of the cytosolic Ca(2+) in podocytes activates Cl(-) channels in podocytes in vivo and in vitro, resulting in a depolarization of podocytes. In vitro studies have shown that in addition to Ca(2+)-activated Cl(-) channels, cAMP-activated Cl(-) channels and Ca(2+)-activated K(+) channels are present in cultured podocytes. The characterization of the signaling pathways that regulate ion channels in podocytes may be important in the understanding of the regulation of the ultrafiltration coefficient K(f). This review summarizes the currently known electrophysiological properties of podocytes.

Single-Channel Analysis of TRPC Channels in the Podocytes of Freshly Isolated Glomeruli

“…Glomerular podocytes are the central components of the renal filtration barrier. Podocytes are very dynamic cells which, at least in part, play a role in the pathogenesis of most proteinuric glomerulopathies (1, 2). …”

“…The lack of such studies has not been a result of their unimportance, but rather resulted from the fact that electrophysiological recording of endogenous ion channels in their native surrounding is a complicated procedure requiring a combination of pure isolation of glomeruli, separation of endogenous currents, electrophysiological skills, etc. Gloy et al, who have developed a technique allowing to measure membrane voltages and ion conductances of podocytes in isolated glomeruli (20), stated later describing the approach they developed that “it is important to develop new methods that better reflect the in vivo situation of podocytes, but studying podocytes function in situ is methodologically very difficult” (2). …”

“…Taking into account the emerging need to comprehend the functionality of ion channels of the podocytes, we have attempted to perform single-channel analysis of endogenous TRPC-like ion channels in the podocytes of isolated decapsulated glomeruli on the basis of the technique suggested by Gloy and colleagues (2, 20). The method described here consists of several steps including removal and perfusion of the rat kidney, isolation of the glomeruli fraction by sequentially pushing the kidney cortex through the steel sieves of different mesh, preparation of the glomeruli for patch-clamping, and electrophysiological cell-attached recordings themselves.…”

Human Podocytes Possess a Stretch-Sensitive, Ca2+-Activated K+ Channel

“…To date, published work has been limited to measurements of the membrane potential and whole-cell conductance in rodent podocytes and their response to vasoactive agonists (5). The membrane potential lies between Ϫ38 and Ϫ64 mV (6,7), suggesting moderate K ϩ selectivity but also the presence of other conductances, such as Cl Ϫ or nonselective cation channels.…”

Role of calcium-phosphorous disorders in the progression of renal failure

“…In these cells, PTH and PTHrp selectively increase cellular cyclic adenosine monophosphate (cAMP) without any change in Ca ++ . cAMP, in turn, has been shown to activate specific Cl − channels in such podocytes [11]. As shown in prostaglandin-induced changes in cAMP, this may well result in alterations of the cytoskeleton and in functional changes of podocytes [12].…”