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Rp-adenosine 3',5'-cyclic monophosphate/PKA

Dear colleagues,

my project involves up-modulation of ion channel currents by cAMP.  Channel activity in our system is increased by membrane-permeable analogs of cAMP, an effect which is thought to be due to activation of PKA.  

However, we noted recently that intracellular application of Rp-cAMPS (in an attempt to block PKA) does not have the anticipated effect.  In our experiments intracellular application Rp-cAMP appears to have has the same (facilitatory) effect on the whole-cell current as extracellular application of dibromo-cAMP would.  Could this mean that Rp-cAMP is acting directly on the channels (as an analog of cAMP) without the involvement of PKA, or is there another more plausible interpretation of this observation?  

Can you please suggest any control experiments, other than mixing Rp-cAMP and Sp-cAMP and looking for additivity of the effects?

Best regards,

I would appreciate your thoughts.

Thomas K. Baumann, Ph.D.
Associate Professor 
Department of Neurological Surgery, L472
& Department of Physiology and Pharmacology
Oregon Health Sciences University
3181 SW Sam Jackson Park Road
Portland, OR 97201-3098, U.S.A.

e-mail: baumannt@ohsu.edu
FAX (503) 494-7161
voice (503) 494-4985