Effects of the endogenous cannabinoid anandamide on voltage‐dependent sodium and calcium channels in rat ventricular myocytes. (July 2014)

• Record Type: Journal Article
• Authors: Al Kury, Lina T; Voitychuk, Oleg I; Yang, Keun‐Hang Susan; Thayyullathil, Faisal T; Doroshenko, Petro; Ramez, Ali M; Shuba, Yaroslav M; Galadari, Sehamuddin; Howarth, Frank Christopher; Oz, Murat
• Is Part Of: British journal of pharmacology. Volume 171:Number 14(2014:Jul.)
• Page Start: 3485
• Page End: 3498
• Publication Date: 2014-07
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12734
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12734-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>The endocannabinoid anandamide (N‐arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes.</p> </sec> <sec id="bph12734-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>Whole‐cell patch‐clamp technique and radioligand‐binding methods were used to analyse the effects of anandamide in rat ventricular myocytes.</p> </sec> <sec id="bph12734-sec-0003" sec-type="section"> <title>Key Results</title> <p>In the presence of 1–10 μM AEA, suppression of both Na<sup>+</sup> and L‐type Ca<sup>2+</sup> channels was observed. Inhibition of Na<sup>+</sup> channels was voltage and <italic>Pertussis</italic> toxin (PTX) – independent. Radioligand‐binding studies indicated that specific binding of [<sup>3</sup>H] batrachotoxin (BTX) to ventricular muscle membranes was also inhibited significantly by 10 μM metAEA, a non‐metabolized AEA analogue, with a marked decrease in B<sub>max</sub> values but no change in K<sub>d</sub>. Further studies on L‐type Ca<sup>2+</sup> channels indicated that AEA potently inhibited these channels (IC<sub>50</sub> 0.1 μM) in a voltage‐ and PTX‐independent manner. AEA inhibited maximal amplitudes without affecting the kinetics of Ba<sup>2+</sup> currents. MetAEA also inhibited Na<sup>+</sup> and L‐type Ca<sup>2+</sup> currents. Radioligand studies indicated that specific binding of [<sup>3</sup>H]isradipine, was inhibited significantly by metAEA. (10 μM), changing B<sub>max</sub> but not K<sub>d</sub>.</p> </sec> <sec id="bph12734-sec-0004" sec-type="section"> <title>Conclusion and Implications</title> <p>Results indicate that AEA inhibited the function of voltage‐dependent Na<sup>+</sup> and L‐type Ca<sup>2+</sup> channels in rat ventricular myocytes, independent of CB<sub>1</sub> and CB<sub>2</sub> receptor activation.</p> </sec> </abstract>