Fig. 1.

The mathematically modelled pathway from SPGN excitation to smooth muscle cell activation. The mathematically modelled pathway from SPGN excitation to smooth muscle cell activation. (A) The model of a SPGN from Briant et al. (2014). Action potentials propagate down the SPGN axon to the postganglionic terminal. (B) This activates I_L and I_N, triggering the influx of calcium into the postganglionic terminal, increasing ${[{\mathrm{Ca}}^{2+}]}_{\mathit{syn}}$. Four molecules of intracellular calcium bind to a fusion protein, activating it (F_A). Once activated, the fusion protein can bind to, and consequently activate, a vesicle V. The activated vesicles, V_A, are assumed to be pre-docked to the synaptic membrane; once activated, it immediately releases its NA contents into the cleft. (C₁) Released noradrenaline activates α₁Rs on the SMC membrane, activating a G-protein (G). This G-protein, drives the hydrolysis of PIP₂. Hydrolysed PIP2 cleaves to form IP3, which activates an IP₃R located on the membrane of the SR. Activation of this receptor causes an efflux of Ca²⁺ from the SR (J_IP3), increasing ${[{\mathrm{Ca}}^{2+}]}_{\mathit{SMC}}$. These receptors also have inactivation and activation sites for ${[{\mathrm{Ca}}^{2+}]}_{\mathit{SMC}}$. Fluxes of Ca²⁺ across the SR membrane also exist due to leakage (J_leak) and calcium pumps (J_pump). (C₂) The intra-SMC matrix contains actin (A) and myosin (M) filaments. At rest these filaments are in a detached state, $A+M$. When the myosin heads are phosphorylated by calcium (M_P), they able to attach to the actin filaments, yielding the state AM_P—a cross-bridge. This cross-bridge can then conduct a ‘power stroke’, sliding the actin filament and producing a contractile force.