title: Control of the propagation of dendritic low-threshold Ca(2+) spikes in Purkinje cells from rat cerebellar slice cultures.
abstract: To investigate the ionic mechanisms controlling the dendrosomatic propagation of low-threshold Ca(2+) spikes (LTS) in Purkinje cells (PCs), somatically evoked discharges of action potentials (APs) were recorded under current-clamp conditions. The whole-cell configuration of the patch-clamp method was used in PCs from rat cerebellar slice cultures. Full blockade of the P/Q-type Ca(2+) current revealed slow but transient depolarizations associated with bursts of fast Na(+) APs. These can occur as a single isolated event at the onset of current injection, or repetitively (i.e. a slow complex burst). The initial transient depolarization was identified as an LTS Blockade of P/Q-type Ca(2+) channels increased the likelihood of recording Ca(2+) spikes at the soma by promoting dendrosomatic propagation. Slow rhythmic depolarizations shared several properties with the LTS (kinetics, activation/inactivation, calcium dependency and dendritic origin), suggesting that they correspond to repetitively activated dendritic LTS, which reach the soma when P/Q channels are blocked. Somatic LTS and slow complex burst activity were also induced by K(+) channel blockers such as TEA (2.5 x 10(-4) M) charybdotoxin (CTX, 10(-5) M), rIberiotoxin (10(-7) M), and 4-aminopyridine (4-AP, 10(-3) M), but not by apamin (10(-4) M). In the presence of 4-AP, slow complex burst activity occurred even at hyperpolarized potentials (-80 mV). In conclusion, we suggest that the propagation of dendritic LTS is controlled directly by 4-AP-sensitive K(+) channels, and indirectly modulated by activation of calcium-activated K(+) (BK) channels via P/Q-mediated Ca(2+) entry. The slow complex burst resembles strikingly the complex spike elicited by climbing fibre stimulation, and we therefore propose, as a hypothesis, that dendrosomatic propagation of the LTS could underlie the complex spike.
authors.affiliation: Laboratoire de Neurotransmission et Sécrétion Neuroendocrine, CNRS UPR 2356, Centre de Neurochimie, 5 rue Blaise Pascal, F-67084 Strasbourg Cedex, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Cavelier
authors.forename: Frederic
authors.initials: F
authors.lastname: Pouille
authors.forename: Thomas
authors.initials: T
authors.lastname: Desplantez
authors.forename: Huguette
authors.initials: H
authors.lastname: Beekenkamp
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bossu
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D060848:Agatoxins; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020865:Calcium Channels, P-Type / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011689:Purkinje Cells / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D060848:Agatoxins; D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D002614:Chelating Agents; D026902:Potassium Channel Blockers; D013111:Spider Venoms; C083855:omega-agatoxin-Aa4b; D002104:Cadmium; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D013779:Tetrodotoxin; D004533:Egtazic Acid; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D002118:Calcium