Calmodulin antagonists depress calcium and potassium currents in ventricular and vascular myocytes.
Myocytes isolated from guinea pig ventricles or bovine portal veins were voltage clamped with a single patch electrode. The calmodulin antagonists (CaM-A) calmidazolium, trifluoperazine (TFP), and chlorpromazine acted as Ca antagonists; they reduced the calcium inward current ICa in a voltage- and use-dependent way. For ventricular myocytes, 50% effective concentration (EC50) of calmidazolium was 1 microM, and the EC50 for TFP was 2.5 microM. For vascular myocytes, these numbers were 0.3 and 1 microM, respectively. CaM-A moderately retarded the inactivation time course and shifted the ICa availability curve to more negative potentials. CaM-A were not selective Ca antagonists; other membrane currents such as sodium currents and inwardly and delayed potassium currents were reduced as well (EC50 between 5 and 10 microM). It is unlikely that the above effects require binding of CaM-A to Ca-calmodulin, since reduction of ICa or potassium current (IK) was not modified when 1) the cells were loaded with 100 microM exogenous calmodulin or 2) Ca ions were removed from the extra- and intracellular space. Instead, the unspecific reduction of membrane currents may result from a change in the lipids of the sarcolemma into which CaM-A partition and accumulate.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002417:Cattle; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011169:Portal Vein; D011188:Potassium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D007093:Imidazoles; D007473:Ion Channels; D014268:Trifluoperazine; D013779:Tetrodotoxin; C031938:calmidazolium; D011188:Potassium; D002118:Calcium