Opposing Actions of cGMP and Calcium on the Conductance of the F0 Subunit c Pore

Subunit c of ATP synthase can be purified from neuronal plasma membrane and from the inner mitochondrial membrane. In the latter location the hydrophobic 75 amino acid protein is one component of the F1 F0 ATP synthase complex but in the former it is alone as a pore that is capable of generating spontaneous electrical oscillations. Pure mammalian subunit c when reconstituted in lipid bilayers and voltage clamped, yields a voltage sensitive pore that conducts a cation current regulated by calcium. The current is here found to be activated by cGMP with a KM ranging from 14 nM to 19 μM depending on calcium and temperature. It is sensitively inhibited by a number of ligands. The KI for calcium ranges from 100 nM to 100 μM depending on cGMP and temperature. DCCD inhibits with a Kapp of 100 nM. The polyamine nicotine inhibits at 84 nM. The pore has properties that would allow it to deliver sodium or calcium through the cell membrane in a controlled manner while maintaining membrane polarization.