Electrophysiology in nanoscale compartments

Voltage-gated ion channels play important roles in many membrane-enclosed structures, including synaptic vesicles, endosomes, mitochondria, chloroplasts, viruses, and bacteria. Here, we study how compartment size and channel gating interact to shape voltage dynamics and ion content in sub-micron structures. In small compartments, assumptions underlying conductance-based (Hodgkin–Huxley type) models of membrane voltage must be relaxed: (1) stochastic gating of individual ion channels can quickly and substantially change membrane voltage; (2) these changes can equilibrate faster than channel state dwell times; and (3) ionic currents, even though as few as two channels, can substantially alter 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_V1.5 in the maturation of macrophage endosomes. The stochastic model predicted dramatically different dynamics compared with a deterministic approach. Electrophysiology of nanoscale structures can be very different from larger structures, even when ion channel composition and density are preserved.