Role of multiple calcium and calcium-dependent conductances in regulation of hippocampal dentate granule cell excitability.
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.
Aradi
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Department of Biological Sciences, Ohio University, Athens 45701, USA. aradi@ohiou.edu
Holmes
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D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D001369:Axons / Q000737:chemistry / Q000502:physiology; D001464:Barium / Q000493:pharmacokinetics; D002021:Buffers; D002118:Calcium / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D003035:Cobalt / Q000494:pharmacology; D003712:Dendrites / Q000737:chemistry / Q000502:physiology; D018891:Dentate Gyrus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D004553:Electric Conductivity; D017097:Electric Impedance; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008959:Models, Neurological; D009474:Neurons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D009532:Nickel / Q000494:pharmacology; D010507:Periodicity; D015221:Potassium Channels / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D012964:Sodium / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002021:Buffers; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D015222:Sodium Channels; D001464:Barium; D003035:Cobalt; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D009532:Nickel; D012964:Sodium; D015761:4-Aminopyridine; D002118:Calcium