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Review
, 4 (6), 475-82

Contributions of T-type Calcium Channel Isoforms to Neuronal Firing

Affiliations
Review

Contributions of T-type Calcium Channel Isoforms to Neuronal Firing

Stuart M Cain et al. Channels (Austin).

Abstract

Low voltage-activated (LVA) T-type calcium channels play critical roles in the excitability of many cell types and are a focus of research aimed both at understanding the physiological basis of calcium channel-dependent signaling and the underlying pathophysiology associated with hyperexcitability disorders such as epilepsy. These channels play a critical role towards neuronal firing in both conducting calcium ions during action potentials and also in switching neurons between distinct modes of firing. In this review the properties of the CaV3.1, CaV3.2 and CaV3.3 T-type channel isoforms is discussed in relation to their individual contributions to action potentials during burst and tonic firing states as well their roles in switching between firing states.

Figures

Figure 1
Figure 1
T-type activity control over neuronal firing patterns. Recordings from reticular thalamic (A and B) and thalamic lateral geniculate (C) neurons displaying altered firing properties depending on the level of contribution from T-type currents. (A) Neurons with a depolarized membrane potential (and therefore inactivated T-type channels) or neurons that have a low level of expression of T-type channels are more likely to fire single or tonic action potentials. T-type channels will conduct calcium during single or tonic action potentials if the firing occurs from a sufficiently hyperpolarized membrane potential and if the expression density is too low to induce burst firing. (B) Burst firing will occur if a high density of T-type channels are present and the neuron is held at a hyperpolarized membrane potential to ensure T-type channels are not inactivated. (C) Slow oscillations occur as a result of bistability of particular neurons depending on whether the window current is “on” or “off”, however this is also highly dependent on leak potassium and the non-specific cationic conductances Ih and ICAN. (C) Redrawn with permission: Hughes et al. Neuron 2004; 42:253–68.
Figure 2
Figure 2
Basic biophysical properties of T-type calcium channels. (A) Representative currents, (B) conductance and inactivation profiles, (C) representative deactivating currents and (D) recovery from inactivation properties of cloned CaV3.1, CaV3.2 and CaV3.3 T-type channels exogenously expressed in HEK293 cells. (E) Table summarizing mean kinetic properties of the three T-subtypes at representative voltages. Redrawn with permission: Chemin et al. J Physiol 2002; 540:3–14.
Figure 3
Figure 3
T-type calcium channel conductance during action potentials. (A) Response of CaV3.1, CaV3.2 and CaV3.3 T-type channels to mock action potentials at varying holding potentials. (B) Response of T-subtypes to mock action potentials with altered repolarization rates summarized with respect to current amplitude and charge transference. (C, left parts) Response of T-subtypes to action potential waveforms recorded from Purkinje neurons during repetitive tonic firing. (C, right parts) Summarized mean data from (C, left part) with respect calcium entry and maximum amplitude of T-current during tonic action potential firing. All figures display results from cloned T-type channels expressed in HEK293 cells. (A and B) Redrawn with permission: Kozlov et al. Eur J Neurosci 1999; 11:4149–58. (C) Redrawn with permission: Chemin et al. J Physiol 2002; 540:3–14.
Figure 4
Figure 4
T-type calcium channel conductance during burst firing and slow oscillations. (A) In a computer generated model of a thalamocortical neuron the native T-type current was replaced with biophysical parameters of each of the cloned CaV3.1, CaV3.2 and CaV3.3 T-type currents determined from experiments in HEK293 cells. CaV3.1 generated short bursts, CaV3.2 slightly longer bursts and CaV3.3 very long sustained bursts (A, upper parts), each correlating with the current generated by the particular subtypes (A, bottom parts). (B, top left part) Schematic of typical T-type activation and inactivation graphs with window current highlighted in grey. (B, bottom left part) Diagram representing the bistable neuronal membrane potential as a result of the interplay between leak potassium conductances and the T-type window calcium conductance. (B, right parts) Schematics describing the activity of the hyperpolarization-activated sodium/potassium conductances (Ih), the calcium-activated non-specific cation conductance (ICAN) and T-type window calcium conductance during slow oscillations. (A) Redrawn with permission: Chemin et al. J Physiol 2002; 540:3–14. (B) Redrawn with permission: Crunelli et al. J Physiol 2005; 62:121–9.

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