Activation by high ambient glucose of large ca2+-activated k+ channels ibk(Ci) in human mesangial cells

Meredith Silverman, James D. Stockand, Steven C. Sansom

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2 Scopus citations

Abstract

Mesangial cells (MO, microvascular pericytes that regulate capillary surface area, and thus glomerular filtration rate (GFR), contract in response to vasoconstricting agonists such as angiotensin II (All). High ambient glucose, which is thought to result in the pathology of diabetic hyperfiltration (DH), has been identified as an inhibitor of MC contraction; however, the mechanism is poorly understood. It was recently shown that BK(Ca) partly regulate MC contraction by hyperpolarizing the membrane in a feedback manner in response to All (Stockand and Sansom, AJP:Cell, 19941. To determine the role of BK(Ca) in DH, we used a contraction assay and patch-clamp methods to characterize its response to All in high glucose (H6). In the contraction assay, MC were incubated for 24 hrs. in either control, HG (20 mM), an osmotic control of high mannitol 120 mM), or HG and charybdotoxin (ChTX; 100 nM). The contractile response to All was attenuated in HG but not in mannitol; attenuation by HG was reversed fay ChTX, suggesting that HG leads to the activation of BK(Ca). In excised, outside-out patches BK(Ca) was completely inhibited by ChTX. When HMC were incubated in control, BK(Ca) in cell attached patches were activated from <0.05 to 0.23 |n-4|; in contrast, when incubated in HG, we found that BKICa) was significantly |P0 - 0.67, n-3) more responsive to All. However, the number of BK(Ca) from HG cells observed in response to All did not increase. We conclude that attenuation of MC contraction in HG is due to enhanced activation of BKICa). These results may partly explain the pathology of DH.

Original languageEnglish (US)
Pages (from-to)A545
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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