Correlation studies of open and closed states fluctuations in an ion channel: Analysis of ion current through a large conductance locust potassium channel

Ion current fluctuations occurring within open and closed states of large conductance locust potassium channel (BK channel) were investigated for the existence of correlation. Both time series, extracted from the ion current signal, were studied by the autocorrelation function (AFA) and the detrended fluctuation analysis (DFA) methods. The persistent character of the short- and middle-range correlations of time series is shown by the slow decay of the autocorrelation function. The DFA exponent $\alpha$ is significantly larger than 0.5. The existence of strongly-persistent long-range correlations was detected only for closed-states fluctuations, with $\alpha=0.98\pm0.02$. The long-range correlation of the BK channel action is therefore determined by the character of closed states. The main outcome of this study is that the memory effect is present not only between successive conducting states of the channel but also independently within the open and closed states themselves. As the ion current fluctuations give information about the dynamics of the channel protein, our results point to the correlated character of the protein movement regardless whether the channel is in its open or closed state.Comment: 12 pages, 5 figures; to be published in Phys. Rev.

Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in culture

The variability of quantal size depends on both presynaptic (profile of the neurotransmitter concentration in the cleft) and postsynaptic (number and gating properties of postsynaptic receptors) factors. Here we have examined the possibility that at nonsaturated synapses in cultured hippocampal neurons, changes in both the transmitter concentration peak and its clearance from the synaptic cleft may influence the variability of spontaneous miniature synaptic GABAergic currents (mIPSCs). We found that, in contrast to the slow-off GABA(A) receptor antagonist bicuculline, fast-off competitive antagonists such as SR-95103 and TPMPA differentially blocked small and large mIPSCs. In the presence of flurazepam, a drug believed to increase the affinity of GABA for GABA(A)R, small mIPSCs were enhanced more efficiently than large events. Moreover, the addition of dextran, which increases the viscosity of the extracellular fluid, preferentially increased small mIPSCs with respect to large ones. These observations suggest that changes in the concentration peak and the speed of GABA clearance in the cleft may be an important source of synaptic variability. The study of the correlation between peak amplitude and kinetics of mIPSCs allowed determination of the relative contribution of transmitter peak concentration vs. time of GABA clearance. Small synaptic responses were associated with fast onset and decay kinetics while large amplitude currents were asociated with slow kinetics, indicating a crucial role for GABA synaptic clearance in variability of mIPSCs. By using model simulations we were able to estimate the range of variability of both the concentration and the speed of clearance of the GABA transient in the synaptic cleft