Manwani, Amit
Coauthors(s): Peter Steinmetz (CALTECH)
Mickey London (Hebrew University, Jerusalem)
Christof Koch (CALTECH)

CALTECH
Computation and Neural Systems
Mail code 139-74, CALTECH Pasadena, CA 91125
www.klab.caltech.edu/~quixote


Channel Noise in Excitable Neuronal Membranes

Voltage-gated ion channels in neuronal membranes switch stochastically between different conformational states which may differ greatly in their permeabilities to membrane ionic currents. The trans-membrane voltage couples the independent channel fluctuations through their voltage-dependent transition rates, enabling ensembles of stochastic ion channels to generate a variety of macroscopic behaviors observed in nerve membranes such as resting potentials, action potentials, spontaneous firing and so on. We are interested in studying the intrinsic noise generated by the conductance fluctuations of voltage-gated ionic channels in neuronal membranes. A few previous studies have investigated the effects of stochastic channel fluctuations on trans-membrane voltage dynamics. However, a systematic investigation of relationship between the channel kinetics and the resulting membrane noise has not been done before. Towards this end, we carried out Monte-Carlo simulations of isopotential patches of neuronal membrane containing voltage-gated stochastic Na and K channels. The kinetics of the ion channels were chosen to be discrete Markovian versions of standard schemes reported in the literature (viz., Hodgkin-Huxley, Mainen-Sejnowski, Magee-Johnston and so on). Using extensive numerical simulations, we compared the the channel noise characteristics (magnitude, power spectral densities, amplitude distributions and so on) for the different schemes. However, the kinetic schemes mentioned above, correspond to different nerve membranes and differ significantly from each other across several dimensions (temperature dependence, densities, level of excitability, and so on). In order to understand the role of parameters like channel density, activation/inactivation time constants and so on, in determining neuronal excitability and noise, we systematically varied individual parameters for a canonical kinetic model. For weakly-active membranes (non-spiking for instance), we also derived closed-form expressions for the membrane noise magnitude and spectra and compared them to the Monte-Carlo simulations. This allowed us to determine their range of validity and examine the conditions for which they can be used.