Fig. 6 | Nature Communications

Fig. 6

From: Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP

Fig. 6

Differential subcellular compartmentation of NPR1 and NPR2/cGMP responses. a Spatio-temporal pattern of FRET signals after ANP application shows far-reaching cGMP response after pre-incubation with 100 nM of the PDE2 inhibitor BAY 60-7550. Scale bar, 10 µm. Quantification is in b. b includes also the quantification of experiments shown in Fig. 1d, h. Shown are means ± s.e.m five cells from three mice per condition were analysed. Differences between all three conditions were significant at p = 0.05 for each individual distance value using mixed ANOVA followed by Wald χ2-test. c Immunoblot analysis of phospholamban (PLN) phosphorylation on Ser16 in working hearts perfused with 100 nM ANP with or without 100 nM BAY 60-7550. * P < 0.05, ** P < 0.01, and n.s. not significant by one-way ANOVA. d Schematic diagram illustrating the major findings of the study. NPR2 is widely distributed across the membrane, generating far-reaching cGMP responses. This cGMP pool is under mild control by PDE3 and causes phosphorylation of PLN and troponin I (TnI), leading to negative inotropic and positive lusitropic effects. NPR1 is exclusively found in T-tubules where it generates locally confined cGMP signals restricted in this microdomain by local action of PDE2. This explains why there are no major effects of ANP/NPR1 on cardiac contractility. SR sarcoplasmic reticulum, SERCA SR calcium ATPase

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