Insulin restores the calcium-activated chloride conductance in dedifferentiated renal glomerular mesangial cells from the H-2KB-TSA58 [corrected] transgenic mouse.
The effects of duration in culture were assessed in mesangial cells from the H-2Kb-tsA58 transgenic mouse using the whole-cell configuration of the patch clamp technique. The whole-cell potassium conductance remained constant in cells from passages 8-17 while the chloride conductance was found to decrease in cells after passage 15. This reduction of the chloride conductance, indicating cell dedifferentiation, was the result of complete loss of the calcium-activated component of the conductance and loss of part of the calcium-insensitive component. Insulin, which increases the calcium-sensitivity of the calcium-activated component of the chloride conductance in early passage cells, restored part of the calcium-sensitive component of the chloride conductance in dedifferentiated cells. Vasoactive agonists such as arginine vasopressin and angiotensin II stimulate a chloride-dependent depolarization in mesangial cells that initiates cell contraction. In view of the importance of the chloride flux it is possible that the loss of a significant magnitude of chloride conductance may underlie mesangial cell pathology to some degree. This is supported by data that show insulin can reverse many of the early renal changes observed in diabetic nephropathy and, as shown in this study, that insulin enhances the chloride conductance in dedifferentiated, cultured mesangial cells.
Barber
R D
RD
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QX, UK.
Henderson
R M
RM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D011188:Potassium / Q000378:metabolism
D018118:Chloride Channels; D007328:Insulin; D011188:Potassium; D002118:Calcium