Nucleotide modulation of f-channel activity in rabbit sino-atrial node myocytes.
f-channel nucleotide modulation was investigated in sino-atrial (SA) node cells isolated from rabbit hearts, using an inside-out macropatch configuration. Saturating doses (30 microM) of phosphorothioate derivatives of cAMP, Sp-cAMPS and Rp-cAMPS, were tested on the cAMP-induced shift of I(f) activation. Responses were not altered when Sp-cAMPS was combined with cAMP. When Rp-cAMPS was superfused with subsaturating cAMP concentrations (1-10 microM), it inhibited cAMP-induced I(f) activation shift. cGMP and cIMP reversibly shifted the I(f) conductance-voltage curve to more positive values; however they had a lesser specificity than that of cAMP. The efficacy ranking for I(f) activation by cyclic nucleotides was: cAMP > cGMP > cIMP. Non cyclic nucleotides (ATP, ADP and AMP) failed to change I(f) activation, indicating that the cyclic nature of nucleotides seems to be essential to f-channel modulation. Similarities between f-channels and cyclic nucleotide-gated (CNG) channels are discussed.
Université de Poitiers/CNRS UMR 6558, Bâtiment P, France.
B
B
Renaudon
J
J
Bescond
P
P
Bois
J
J
Lenfant
D000818:Animals; D016275:Atrial Function; D001665:Binding Sites; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D007289:Cyclic IMP / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D011817:Rabbits
D007473:Ion Channels; D007289:Cyclic IMP; D000242:Cyclic AMP; D006152:Cyclic GMP