K201 Still Active With AIP

The drug K201 (JTV-519) is a 1, 4 benzothiazepine derivative which is known to be a Ca2+ channel antagonist. Previous studies have shown that K201 inhibits the activity of Sarcoplasmic Reticulam (SR) Ca2+-ATPase (SERCA) thereby showing a declined Ca2+ uptake by SR. The aim of this study was to find the effect of K201 on Ca2+ uptake by normal rabbit cardiac Myocytes and also to reveal the effect of Autocamtide-2 related Inhibitory Peptide myristoylated (AIP), which is a CaM Kinase II inhibitor.

The protocol involved challenging oxalate-equilibrated SR with repeated doses of Ca2+ with different concentration of drug K201. The cells were subjected to test the role of CaMKII by incubating in two different concentrations of AIP (5μM and 15 μM). All the experiments had a standard Ca2+ run to compare the differences in the Ca2+ up taking. The results showed that K201 did not inhibit SERCA significantly at 3μM. But when cells were incubated with 5μM AIP the drug K201 inhibited SERCA. However at higher concentration of AIP (15μM), the drug K201 did not showed any significant effect. This study suggests that inhibition of CaMKinase facilitates the inhibition of SERCA by K201.

Jayanth, 2007

Jayanth, 2007

Original Post: researchers.blogspot.com

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