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Action of niflumic acid on evoked and spontaneous calcium‐activated chloride and potassium currents in smooth muscle cells from rabbit portal vein
Author(s) -
Hogg R.C.,
Wang Q.,
Large W.A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13177.x
Subject(s) - niflumic acid , chemistry , potassium , calcium , tetraethylammonium chloride , biochemistry , organic chemistry
1 The action of niflumic acid was studied on spontaneous and evoked calcium‐activated chloride ( I Cl(Ca) ) and potassium ( I K(Ca) ) currents in rabbit isolated portal vein cells. 2 With the nystatin perforated patch technique in potassium‐containing solutions at a holding potential of – 77 mV (the potassium equilibrium potential), niflumic acid produced a concentration‐dependent inhibition of spontaneous transient inward current (STIC, calcium‐activated chloride current) amplitude. The concentration to reduce the STIC amplitude by 50% (IC 50 ) was 3.6 × 10 −6 m . 3 At – 77 mV holding potential, niflumic acid converted the STIC decay from a single exponential to 2 exponential components. In niflumic acid the fast component of decay was faster, and the slow component was slower than the control decay time constant. Increasing the concentration of niflumic acid enhanced the decay rate of the fast component and reduced the decay rate of the slow component. 4 The effect of niflumic acid on STIC amplitude was voltage‐dependent and at – 50 and + 50 mV the IC 50 values were 2.3 × 10 − 6 m and 1.1 × 10 −6 m respectively (cf. 3.6 × 10 −6 m at −77 mV). 5 In K‐free solutions at potentials of – 50 mV and + 50 mV, niflumic acid did not induce a dual exponential STIC decay but just increased the decay time constant at both potentials in a concentration‐dependent manner. 6 Niflumic acid, in concentrations up to 5 × 10 −5 m , had no effect on spontaneous calcium‐activated potassium currents. 7 Niflumic acid inhibited noradrenaline‐ and caffeine‐evoked I Cl(Ca) with an IC 50 of 6.6 × 10 −6 m , i.e. was less potent against evoked currents compared to spontaneous currents. In contrast niflumic acid (2 × 10 −6 m –5 × 10 −5 m ) increased noradrenaline‐ and caffeine‐induced I K(Ca) . 8 The results are discussed with respect to the mechanism of block of I Cl(Ca) by niflumic acid and its suitability as a pharmacological tool for assessing the role of I Cl(Ca) in physiological mechanisms.