Investigations of cytoplasmic contractile and cytoskeletal elements in the kidney glomerulus

Investigations of cytosplasmic contractile and cytoskeletal elements in the kidney glomerulus. Electron microscopy and in vitro techniques were used to evaluate the morphologic responses of glomerular podocytes and glomerular endothelial cells to compounds that affect either cytoplasmic contractile elements or cytoplasmic microtubules. In response to in vitro incubation in the presence of cytochalasin D or B (compounds that inhibit contraction of actin-like microfilaments), podocyte foot processes change in shape from short processes with broad bases to taller processes with narrow bases. Coincident with these shape changes, there is an increase in the number of fully patent filtration slit spaces between adjacent foot processes. In view of these observations, it is proposed that glomerular podocytes have the potential for monitoring the filtration slit area available for solute efflux across the glomerular wall by modifying the shapes of their foot processes (that is, expanding and contracting the bases of these structures). As in vitro incubation continues for 1 to 2 days, the cytochalasins inhibit the shape changes of glomerular podocytes that normally occur during 2 days of in vitro incubation—the loss of foot processes, filtration slits, endothelial pores, and thickening of the endothelium. The cytochalasins also inhibit the loss of foot processes and filtration slits that otherwise occur in response to enzymatic removal of glomerular-free surface sialic acid. The in vitro depolymerization of glomerular microtubules by any of a variety of drugs (for example, vinblastine sulfate, colchicine) results in the rounding up of podocyte cell bodies, the thinning of podocyte major processes, and a partial collapsing of the glomerular endothelial walls. These latter observations suggest that microtubules play an important cytoskeletal role in maintaining the structural integrity of these cells. Etude des elements contractiles et cytosquelettiques dans le glomerule renal. La microscopie electronique et les techniques in vitro ont ete utilisees pour evaluer le reponse morphologique des podocytes glomerulaires et des cellules endotheliales glomerulaires a des composes qui affectent les elements contractiles du cytoplasme ou les microtubules. En reponse a l'incubation in vitro en presence de cytochalasine D ou B (des composes qui inhibent la contraction des microfilaments semblables a l'actine), les processus pedicules changent de forme et passent de celle des processus courts a bases larges a des processus longs a bases etroites. En meme temps que les modifications de forme il y a une augmentation dans le nombre des fentes de filtration totalement permeables entre des processus adjacents. En fonction de ces observations il est propose que les podocytes glomerulaires ont la capacite de moduler la surface de fentes de filtration disponible pour l'efflux a travers la paroi glomerulaire en modifiant la forme des processus pedicules (c'est-a-dire en etendant ou en contractant la base de ces structures). Quand l'incubation est poursuivie pendant un ou deux jours, les cytochalasines inhibent les modifications de forme des podocytes glomerulaires, la perte des processus pedicules, des fentes de filtration, des pores endotheliaux et l'epaississement de l'endothelium qui prennent place normalement dans les deux jours d'incubation in vitro. Les cytochalasines inhibent aussi la perte des processus et des fentes de filtration qui sont observes en reponse a la soustraction enzymatique de l'acide sialique libre a la surface des glomerules. La depolymerisation in vitro des microtubules glomerulaires par une serie de drogues (sulfate de vinblastine, colchicine) a pour resultat la transformation des corps cellulaires des podocytes, l'amincissement des processus principaux des podocytes et l'effondrement partiel des parois endotheliales des glomerules. Ces dernieres observations suggerent que les microtubules jouent un role important de cytosquelette en maintenant l'integrite structurale des cellules.