Intracellular injection of cyclic GMP depresses cardiac slow action potentials.
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.
Wahler
G M
GM
Sperelakis
N
N
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
D006152:Cyclic GMP