Low-threshold potassium channels and a low-threshold calcium channel regulate Ca2+ spike firing in the dendrites of cerebellar Purkinje neurons: a modeling study.
Various types of voltage-gated ion channels are distributed along the dendrites of neurons in the central nervous system. We have recently shown experimentally that the dendrites of cerebellar Purkinje neurons contain low-threshold voltage-gated Ca(2+) channels and low-threshold voltage-gated K+ channels. Although we found that these channels are involved in regulating the onset of Ca(2+)-dependent action potentials in the dendrites, we were unable to identify which of the known types of low-threshold Ca2+ channels and K+ channels were responsible, since there was no reliable method of discriminating between them. Here, we have built a detailed compartmental model of a Purkinje neuron by incorporating two types of low-threshold Ca2+ channel (T-type and class-E, or R-type) and two types of low-threshold K+ channel (A-type and D-type), in addition to another eight voltage-gated channel types, using a compartmental model neuron simulator. The model reproduces the basic features of the depolarization-induced responses of Purkinje neurons, such as fast Na+ spikes in the soma, Ca2+ spikes in the dendrites, the slow onset of Ca2+ spikes, repetitive Ca2+ spikes in the presence of TTX, the marked shortening of Ca2+ spike onset in the presence of 4-aminopydridine, and the longer Ca2+ spike onset in the presence of Ni2+. Our model shows that the D-type K+ channel and the class-E Ca2+ channel regulate the onset of depolarization-induced Ca2+ spikes in Purkinje neurons. These channels might be involved in integrating synaptic inputs in Purkinje neurons.
Miyasho
T
T
Department of Physics, School of Science and Engineering, Waseda University, Shinjyuku-ku, 169, Tokyo, Japan.
Takagi
H
H
Suzuki
H
H
Watanabe
S
S
Inoue
M
M
Kudo
Y
Y
Miyakawa
H
H
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008959:Models, Neurological; D009532:Nickel / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015203:Reproducibility of Results; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D015220:Calcium Channels; D015221:Potassium Channels; D013779:Tetrodotoxin; D009532:Nickel; D002118:Calcium