Figure 2.

Our conceptual model demonstrates that in ASM cells, excitation, contraction, and energy production are coupled with two mechanisms. (1) On a shorter timescale, agonist-induced elevation of [Ca²⁺]_cyt triggers activation of the mitochondrial Ca²⁺ uniporter (MCU) and Ca²⁺ influx, which increases tricarboxylic acid cycle (TCA) activity thereby providing H⁺ to the electron transport chain (ETC). (2) On a longer timescale, agonist-induced force/contraction results in ATP consumption and an increase in ADP, which increases ADP influx into mitochondria via the adenosine nucleotide transporter (ANT), stimulating ATP synthase (F1Fo-ATPase) activity. With excessive mitochondrial Ca²⁺ influx, an overload in mitochondrial Ca²⁺ concentration ([Ca²⁺]_mit) can trigger the opening of mitochondrial permeability transition pores (mPTP), which are large conductance channels present in the inner mitochondrial membrane that reduce the H⁺ gradient and mitochondrial membrane potential (Δψ_m).