Figure 10.
M-current effects on EPSP summation in a CA1 pyramidal neuron model. A, Left, A series of steady-state activation curves as reported by Wang et al. (1998) and Wickenden et al. (2000). “Wang native” (black line) refers to the kinetics of native IM recorded from sympathetic neurons. “Wang expressed” (black dots) refers to expressed KCNQ2 and KCNQ3 channels in oocytes. “Wickenden control” (blue line) refers to expressed KCNQ2 and KCNQ3 channels in CHO cells, and “Wickenden retigabine” (blue dots) refers to KCNQ2/3 in CHO cells with 10 μm retigabine in the extracellular medium. In B, E, and F, “Wang native” was used. A, Right, Voltage dependence of the time constants of activation and deactivation. B, Voltage-clamp simulations at the soma, by stepping the voltage from −70 to −20 mV in 10 mV steps. For each voltage step, the difference in current response before and after removing IM from the model is shown. C, In the diagram, red indicates the presence of IM in the soma, axon hillock, initial segment, and axon nodes. A synaptic conductance in the apical dendrite 300 μm from the soma was activated 11 times at 50 Hz. Somatic voltage responses for IM with different kinetics (compare with A) are shown. D, The same synapse as in C was activated once, and the effects of IM on the somatic EPSP are shown, for different IM kinetics (compare with A). E, Effects of different IM distributions on synaptic summation. The synaptic stimulation was the same as in C. (1), Red indicates a uniform density of IM in all compartments except the myelinated axon segments. (2), IM was removed from the “perisomatic” region, i.e., from the soma, axon hillock, initial segment, and the first 50 μm of the proximal dendrites. (3), Model with no IM. F, Left shows the time constant of activation and deactivation for three different simulation temperatures. Right shows the effects of varying the simulation temperature on the somatic voltage in response to a series of EPSPs, evoked as in C.