title: Minimal alterations in T-type calcium channel gating markedly modify physiological firing dynamics.
abstract: T-type calcium channel isoforms expressed in heterologous systems demonstrate marked differences in the biophysical properties of the resulting calcium currents. Such heterogeneity in gating behaviour not only reflects structural differences but is also observed following the regulation of channel activity by a number of ligands. However, the physiological impact of these differences in gating parameters of the T channels has never been evaluated in situ where the unique interplay between T-type calcium and other intrinsic currents is conserved, and T channel activation can be triggered by synaptic stimulation. Here, using the dynamic clamp technique, artificial T conductances were re-incorporated in thalamic neurons devoid of endogenous T currents to dissect the physiological role of the T current gating diversity on neuronal excitability. We demonstrate that the specific kinetics of the T currents in thalamocortical and nucleus reticularis thalami neurons determine the characteristic firing patterns of these neurons. We show that subtle modifications in T channel gating that are at the limit of the resolution achieved in classical biophysical studies in heterologous expression systems have profound consequences for synaptically evoked firing dynamics in native neurons. Moreover, we demonstrate that the biophysical properties of the T current in the voltage region corresponding to the foot of the activation and inactivation curves drastically condition physiologically evoked burst firing with a high degree of synaptic input specificity.
authors.affiliation: UPMC Université Paris 6, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Tscherter
authors.forename: F
authors.initials: F
authors.lastname: David
authors.forename: T
authors.initials: T
authors.lastname: Ivanova
authors.forename: C
authors.initials: C
authors.lastname: Deleuze
authors.forename: J J
authors.initials: JJ
authors.lastname: Renger
authors.forename: V N
authors.initials: VN
authors.lastname: Uebele
authors.forename: H-S
authors.initials: HS
authors.lastname: Shin
authors.forename: T
authors.initials: T
authors.lastname: Bal
authors.forename: N
authors.initials: N
authors.lastname: Leresche
authors.forename: R C
authors.initials: RC
authors.lastname: Lambert
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020013:Calcium Signaling; D055724:Electrophysiological Phenomena; D005071:Evoked Potentials; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000502:physiology
chemical_list: C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type