Figure 6.

Analysis of coupled-clock mechanisms. Action potential firing rate (% basal) change under the effect of adrenergic receptor (β-AR) stimulation by ISO (A) or cholinergic receptor (ChR) stimulation by CCh (B). In order to highlight the relative contribution of different system components, some mechanisms were virtually deactivated by disabling their modulation by PKA/cAMP. Of note, the RyR modulation by PKA is very minor in the current formulation of the model and thus is left intact for all the runs. SERCA: sarcoplasmic reticulum Ca²⁺ ATPase, PLB: phospholamban. (C) Representative western blots of PLB phosphorylated at serine¹⁶ site and total PLB in rabbit SANC in the basal state and following milrinone (50 μM), phosphodiesters inhibitor (IBMX, 100 μM), β-AR stimulation [0.1 μM (ISO1) or 1 μM (ISO2) isoproterenol], and PKA inhibitor (PKI, 10 μM; reproduce from Vinogradova et al., 2010). (D) Representative western blots of PLB phosphorylated at serine¹⁶ site and total PLB in rabbit SANC in the basal state and following graded concentrations of CCh (Lyashkov et al., 2009).