Inhibition of the calcium-activated chloride current in cardiac ventricular myocytes by N-(p-amylcinnamoyl)anthranilic acid (ACA).
N-(p-amylcinnamoyl)anthranilic acid (ACA), a phospholipase A(2) (PLA(2)) inhibitor, is structurally-related to non-steroidal anti-inflammatory drugs (NSAIDs) of the fenamate group and may also modulate various ion channels. We used the whole-cell, patch-clamp technique at room temperature to investigate the effects of ACA on the Ca(2+)-activated chloride current (I(Cl(Ca))) and other chloride currents in isolated pig cardiac ventricular myocytes. ACA reversibly inhibited I(Cl(Ca)) in a concentration-dependent manner (IC(50)=4.2 μM, n(Hill)=1.1), without affecting the L-type Ca(2+) current. Unlike ACA, the non-selective PLA(2) inhibitor bromophenacyl bromide (BPB; 50 μM) had no effect on I(Cl(Ca)). In addition, the analgesic NSAID structurally-related to ACA, diclofenac (50 μM) also had no effect on I(Cl(Ca)), whereas the current in the same cells could be suppressed by chloride channel blockers flufenamic acid (FFA; 100 μM) or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS;100 μM). Besides I(Cl(Ca)), ACA (50 μM) also suppressed the cAMP-activated chloride current, but to a lesser extent. It is proposed that the inhibitory effects of ACA on I(Cl(Ca)) are PLA(2)-independent and that the drug may serve as a useful tool in understanding the nature and function of cardiac anion channels.
Division of Experimental Cardiac Surgery, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Asfree
A
Gwanyanya
Regina
R
Macianskiene
Virginie
V
Bito
Karin R
KR
Sipido
Johan
J
Vereecke
Kanigula
K
Mubagwa
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D002712:Chlorides / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D064801:Phospholipase A2 Inhibitors; D013552:Swine; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D002712:Chlorides; D002934:Cinnamates; D004791:Enzyme Inhibitors; D064801:Phospholipase A2 Inhibitors; D062367:ortho-Aminobenzoates; C085901:4-amylcinnamoylanthranilic acid; D002118:Calcium