Are acetylcholine‐induced increases in 42K efflux mediated by intracellular cyclic GMP in turtle cardiac pace‐maker tissue?

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Abstract
42K efflux was measured from small strips of turtle sinus venosus tissue in order to characterize further the phamacology of the acetylcholine response and to test whether cGMP is the intracellular mediator of this response. The 42K wash-out curves show that the fractional escape rate (FER) of 42K efflux is nearly constant after 60-80 min, indicating that after this time period 42K FER is controlled by barrier-limited diffusion from a single intracellular compartment. The threshold of the dose-response relatonship for the acetylcholine[ACh]-induced increase in 42K FER is about 10-8 M and the Km is 2.75 .times. 10-7 in non-eserinized preparations. This ACh response is completely blocked by atropine; but nicotinic blockers produce no detectable reduction of it. Exogenous application of lipid-soluble analogues of cGMP (dibutyryl or 8-bromo-cGMP applied at 2-3 mM for 30 min) failed to mimic the Ach-induced augmentation of 42K FER. Experiments in which sodium nitroprusside (5 .times. 10-4 M for 30 min) was applied in order to stimulate the guanylate cyclase and hence produce a large, maintained increase in intracellular cGMP failed to show a signifiant increase in 42K FER. When acetylcholine (10-6 M) was applied in the presence of 0[Ca2+]0 (in an attempt to inhibit the guanylate cyclase) there was no significant reduction in the ACh induced increases in 42K FER. These 3 indirect tests indicate that the muscarinic ACh-induced increase in 42K FER in cardiac pace-marker tissue is unlikely to be mediated entirely by changes in the levels of intracellular cGMP.