Fig. 1

Model of pore former induced lysis. A bacterial toxin inserts a large channel or pore into the erythrocyte membrane. ATP is immediately released through the pore and activates P2X receptors. The membrane insertion of the toxin also causes a steep rise in the intracellular Ca²⁺ concentration ([Ca²⁺]_i), which results from Ca²⁺ passing through the pore itself and from activation of P2X receptors, which are non-selective cation channels permeable to Ca²⁺. The increase in [Ca²⁺]_i activates the Ca²⁺-sensitive K⁺ channel K_Ca3.1 and Cl⁻ channel TMEM16A, which results in K⁺ and Cl⁻ efflux and cell shrinkage as obligated water follows. The cells will remain shrunken as long as the K⁺ efflux surpasses the Na⁺ influx via the toxin pore and the P2X receptors. Prolonged stimulation of P2X₇ can activate pannexins, which will contribute to the Na⁺ influx. Eventually, the Na⁺ influx will exceed the K⁺ efflux and the cells will swell and eventually burst. Blockage of the P2X₁ and P2X₇ receptor has been proven as a protective measure for bacterial toxins, and for complement to carry out their toxicity. The model based on previous work [6, 14, 17, 30]