Modulation of Membrane Electrogenic Transport. The Role of Charge-Dipole Coupling – Eitan Gross

Date: Tue. March 25th, 2003, 12:30 pm-1:30 pm
Location: Rockefeller 221

The behavior of a given ion channel can be different in different regions of a cell. For example, Na+ channels in the axons of nerve cells inactivate much faster then in the cell body (soma). These observations suggest that different regions of the cell could respond differently to the same stimulus without differences in channel surface density between the regions. While the mechanism underlying such spatial variations in channel function are unclear, it is important to realize that the regulatory elements within them (i.e. gating charges) are fundamentally responding to the potential gradient at their specific location in the plasmalemma – the intramembrane electric field. Therefore, structurally similar ion channels might behave differently along the surface of a neuron if the endogenous intramembrane electric field they are experiencing is non-uniform. To address this issue, we developed optical methods to map local variations in intramembrane electric fields along the surface of cells. The method is based on measuring the fluorescence ratio or of the second harmonic generation (SHG) signal from voltage-sensitive (electrochromic) membrane dyes. Using these methods we found that the dipole electric field (~1/r^3) in the membrane is distributed asymmetrically between the soma and the axon. Consequentially, we hypothesize that spatial variations in charge-dipole coupling between the channel’s gating charges and the membrane’s dipole electric field, along the surface of the cell, offset the activation energy of Na+ channels in the axon. These variations might be responsible for the increased sensitivity of the cell’s axons to external guidance cues.