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SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: PHYSIOLOGICAL ROLE OF LARGE, Ca 2+ ‐ACTIVATED K + CHANNELS IN HUMAN GLOMERULAR MESANGIAL CELLS
Author(s) -
Sansom Steven C,
Stockand James D
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb03066.x
Subject(s) - iberiotoxin , bk channel , contraction (grammar) , nitric oxide , biophysics , angiotensin ii , chemistry , medicine , mesangial cell , channel blocker , patch clamp , endocrinology , calcium , membrane potential , potassium channel , biology , electrophysiology , biochemistry , kidney , receptor
SUMMARY1 Contraction assays and patch clamp methods were used to determine the role of K + channels in the regulation of contractile tone of human mesangial cells (MC) in culture. 2 MC contraction was induced by vasoconstrictor agents, such as angiotensin II (AngII; 100nmol/L) and glybenclamide (Glyb), but not by iberiotoxin (IbTX), a blocker of large Ca 2+ ‐activated K + channels (BK(Ca)). These results suggest that Glyb‐sensitive K + channels, but not BK(Ca) channels, were active at rest. 3 In the presence of 100nmol/L IbTX, contraction by Angll was slightly, but not significantly, enhanced, indicating that BK(Ca) has a minimal role as a negative feedback regulator of contraction. Nitroprusside (NP; 100μmol/L), a nitric oxide (NO) donor, atrial natriuretic peptide (ANP; 1.0 μmol/L) and db‐cGMP (10μmol/L) attenuated AngII‐induced contraction in the absence, but not in the presence, of IbTX, suggesting that BK(Ca) channels were activated by cGMP. 4 In patch clamp experiments, three distinct K + ‐selective channels of 9, 65 and 150 pS (outward currents) were found in excised, inside‐out patches. The 150 pS channel was completely inhibited by 100nmol/L IbTX and displayed ***voltage‐ and calcium‐dependent gating qualitatively similar to BK(Ca) in other cell types. 5 In cell attached (CA) patches, the response of BK(Ca) to bath AngII (100nmol/L) was relatively minor in control solutions, but was considerably greater in the presence of db‐cGMP. 6 In excised patches, Mg‐ATP (1 mmol/L) plus db‐cGMP (1 μmol/L) activated BK(Ca) in the absence, but not the presence, of the non‐specific kinase inhibitor, staurosporine. 7 Separate experiments showed that BK(Ca) were also activated by arachidonic acid and high ambient glucose concentrations. 8 These results indicate that: (i) resting MC tone is sensitive to glybenclamide and apamin; and (ii) the role of BK(Ca) as a negative feedback regulator of contraction is minimal under normal conditions but is markedly enhanced by cGMP‐stimulating relaxants and arachidonic acid.