Scientific article

Substance P and bradykinin activate different types of KCa currents to hyperpolarize cultured porcine coronary artery endothelial cells

Published inJournal of physiology, vol. 519, no. 2, p. 361-371
Publication date1999
First online date2004-09-07

  • Substance P and bradykinin, endothelium-dependent vasodilators of pig coronary artery, trigger in endothelial cells a rise in cytosolic Ca2+ concentration ([Ca2+]i) and membrane hyperpolarization. The aim of the present study was to determine the type of Ca2+-dependent K+ (KCa) currents underlying the endothelial cell hyperpolarization.
  • The substance P-induced increase in [Ca2+]i was 30 % smaller than that induced by bradykinin, although the two peptides triggered a membrane hyperpolarization of the same amplitude. The two agonists evoked a large outward K+ current of the same conductance at maximal stimulation. Agonists applied together produced the same maximal current amplitude as either one applied alone.
  • Iberiotoxin (50 nM) reduced by about 40 % the K+ current activated by bradykinin without modifying the substance P response. Conversely, apamin (1 μm) inhibited the substance P-induced K+ current by about 65 %, without affecting the bradykinin response. Similar results were obtained on peptide-induced membrane hyperpolarization.
  • Bradykinin-induced, but not substance P-induced, endothelium-dependent relaxation resistant to NG-nitro-L-arginine and indomethacin was partly inhibited by 3 μm 17-octadecynoic acid (17-ODYA), an inhibitor of cytochrome P450 epoxygenase. Similarly, the bradykinin-induced K+ current was reduced by 17-ODYA.
  • Our results show that responses to substance P and bradykinin result in a hyperpolarization due to activation of different KCa currents. A current consistent with the activation of large conductance (BKCa) channels was activated only by bradykinin, whereas a current consistent with the activation of small conductance (SKCa) channels was stimulated only by substance P. The observation that a similar electrical response is produced by different pools of channels implies distinct intracellular pathways leading to KCa current activation.
  • eng
    Citation (ISO format)
    FRIEDEN, Maud, SOLLINI, Monica, BENY, Jean-Louis. Substance P and bradykinin activate different types of K<sub>Ca</sub> currents to hyperpolarize cultured porcine coronary artery endothelial cells. In: Journal of physiology, 1999, vol. 519, n° 2, p. 361–371. doi: 10.1111/j.1469-7793.1999.0361m.x
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    Article (Published version)
    ISSN of the journal0022-3751

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