NUCLEOTIDE MODULATION OF F-CHANNEL ACTIVITY IN RABBIT SINOATRIAL NODEMYOCYTES

f-channel nucleotide modulation was investigated in sino-atrial (SA) n ode cells isolated from rabbit hearts, using an inside-out macropatch configuration. Saturating doses (30 mu M) of phosphorothioate derivati ves of cAMP, Sp-cAMPS and Rp-cAMPS, were tested on the cAMP-induced sh ift of I-f activation. Responses were not altered when Sp-cAMPS was co mbined with cAMP. When Rp-cAMPS was superfused with subsaturating cAMP concentrations (1-10 mu M), it inhibited cAMP-induced I-f activation shift, cGMP and cIMP reversibly shifted the I-f conductance-voltage cu rve to more positive values; however they had a lesser specificity tha n that of cAMP. The efficacy ranking for I-f activation by cyclic nucl eotides was: cAMP > cGMP > cIMP. Non cyclic nucleotides (ATP, ADP and AMP) failed to change I-f activation, indicating that the cyclic natur e of nucleotides seems to be essential to f-channel modulation. Simila rities between f-channels and cyclic nucleotide-gated (CNG) channels a re discussed.