We have constructed a detailed model of a hippocampal dentate granule (DG) cell that includes nine different channel types. Channel densities and distributions were chosen to reproduce reported physiological responses observed in normal solution and when blockers were applied. The model was used to explore the contribution of each channel type to spiking behavior with particular emphasis on the mechanisms underlying postspike events. T-type calcium current in more distal dendrites contributed prominently to the appearance of the depolarizing after-potential, and its effect was controlled by activation of BK-type calcium-dependent potassium channels. Coactivation and interaction of N-, and/or L-type calcium and AHP currents present in somatic and proximal dendritic regions contributed to the adaptive properties of the model DG cell in response to long-lasting current injection. The model was used to predict changes in channel densities that could lead to epileptogenic burst discharges and to predict the effect of altered buffering capacity on firing behavior. We conclude that the clustered spatial distributions of calcium related channels, the presence of slow delayed rectifier potassium currents in dendrites, and calcium buffering properties, together, might explain the resistance of DG cells to the development of epileptogenic burst discharges.

4-Aminopyridine↗

PubMedDate not supplied

Models of calmodulin trapping and CaM kinase II activation in a dendritic spine.

Activation of calcium/calmodulin-dependent protein kinase II (CaMKII) by calmodulin following calcium entry into the cell is important for long-term potentiation (LTP). Here a model of calmodulin binding and trapping by CaMKII in a dendritic spine was used to estimate levels and durations of CaMKII activation following LTP-inducing tetani. The calcium signal was calcium influx through NMDA receptor channels computed in a highly detailed dentate granule cell model. Calcium could bind to calmodulin and calmodulin to CaMKII. CaMKII subunits were either free, bound with calmodulin, trapped, autonomous, or capped. Strong low-frequency tetanic input produced little calmodulin trapping or CaMKII activation. Strong high-frequency tetanic input caused large numbers of CaMKII subunits to become trapped, and CaMKII was strongly activated. Calmodulin trapping and CaMKII activation were highly dependent on tetanus frequency (particularly between 10 and 100 Hz) and were highly sensitive to relatively small changes in the calcium signal. Repetition of a short high-frequency tetanus was necessary to achieve high levels of CaMKII activation. Three stages of CaMKII activation were found in the model: a short, highly activated stage; an intermediate, moderately active stage; and a long-lasting third stage, whose duration depended on dephosphorylation rates but whose decay rate was faster at low CaMKII activation levels than at high levels. It is not clear which of these three stages is most important for LTP.

Action Potentials↗