title: Intracellular injection of cyclic GMP depresses cardiac slow action potentials.
abstract: Our laboratory has shown that intracellular injection of cyclic AMP (cAMP) transiently enhances slow APs in myocardial cells, presumably by phosphorylating slow channels. To test if cGMP also plays a role in cardiac slow channel function, superfusion with 8-Br-cGMP, and intracellular injections of cGMP were carried out in guinea pig papillary muscles (stimulated at 0.5 Hz at 37 degrees C). In normal (4.7 mM K+) Tyrode's solution, 0.1 mM 8-Br-cGMP depressed contractions and had variable effects on the duration of the fast APs. Slow APs were elicited by electrical stimulation (in 25 mM K+-Tyrode's solution) following the addition of 10 mM TEA and doubling the bath [Ca] (to 4.0 mM) or addition of 0.2 microM isoproterenol. Slow APs are dependent on the slow inward current carried through voltage- and time-dependent slow channels. 8-Br-cGMP (0.1 microM - 1 mM) superfusion depressed or abolished slow APs and accompanying contractions. cGMP (5-100 mM Na+ salt in 0.2 M KC1) was injected by application of pressure pulses (40-75 psi, 1-30 sec duration) to the recording microelectrode. cGMP injection transiently depressed (n = 15) or abolished (n = 4) the slow APs. The effect began 1 min after the onset of the pulse, reached a maximum at 2 min and recovered fully within 5-6 min. Thus, it appears that the intracellular cGMP level can modulate the slow inward current in a direction opposite to that of cAMP. These effects may both be due to cyclic nucleotide-dependent phosphorylations.
authors.forename: G M
authors.initials: GM
authors.lastname: Wahler
authors.forename: N
authors.initials: N
authors.lastname: Sperelakis
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006152:Cyclic GMP / Q000008:administration & dosage* / Q000494:pharmacology; D003864:Depression, Chemical; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007267:Injections; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010766:Phosphorylation
chemical_list: D006152:Cyclic GMP