Electrophysiology in small compartments

Voltage-gated ion channels are found in many membrane-enclosed structures, including synaptic vesicles, endosomes, mitochondria, chloroplasts, viruses and bacteria. In small compartments, assumptions underlying Hodgkin-Huxley-type models must be relaxed: [1] stochastic gating of individual ion channels can substantially change the membrane voltage, even during a single gating event; and [2] ionic currents, even through a single channel, can substantially alter internal ionic concentrations. We adapted conductance-based models to incorporate these effects, and we then simulated voltage dynamics of small vesicles as a function of vesicle radius and channel density. We identified regimes in this parameter space with qualitatively distinct dynamics. We then performed stochastic simulations to explore the role of Na _V 1.5 in maturation of macrophage endosomes. The stochastic model predicted dramatically different dynamics compared to a classical conductance-based approach. Electrophysiology of small structures can be very different from larger structures, even when ion channel composition and density are preserved.