Cell-Type Specific Distribution of T-Type Calcium Currents in Lamina II Neurons of the Rat Spinal Cord

Abstract

Spinal lamina II (substantia gelatinosa, SG) neurons integrate nociceptive information from the primary afferents and are classified according to electrophysiological (tonic firing, delayed firing, single spike, initial burst, phasic firing, gap firing and reluctant firing) or morphological (islet, central, vertical, radial and unclassified) criteria. T-type calcium (Cav3) channels play an essential role in the central mechanism of pathological pain, but the electrophysiological properties and the cell-type specific distribution of T-type channels in SG neurons have not been fully elucidated. To investigate the electrophysiological and morphological features of T-type channel-expressing or -lacking neurons, voltage- and current-clamp recordings were performed on either transverse or parasagittal spinal cord slices. Recording made in transverse spinal cord slices showed that an inward current (IT) was observed in 44.5% of the SG neurons that was fully blocked by Ni2+ and TTA-A2. The amplitude of IT depended on the magnitude and the duration of hyperpolarization pre-pulse. The voltage for eliciting and maximizing IT were −70 mV and −35 mV, respectively. In addition, we found that most of the IT-expressing neurons are tonic firing neurons and exhibit more negative action potential (AP) threshold and smaller difference of AP threshold and resting membrane potential (RMP) than those neurons lacking IT. Consistently, a specific T-type calcium channel blocker TTA-P2 increased the AP threshold and enlarged the difference between AP threshold and membrane potential (Ihold = 0). Meanwhile, the morphological analysis indicated that most of the IT-expressing neurons are islet neurons. In conclusion, we identify a cell-type specific distribution and the function of T-type channels in SG neurons. These findings might provide new insights into the mechanisms underlying the contribution of T-type channels in sensory transmission.

Cav3.2 T-type calcium channels shape electrical firing in mouse Lamina II neurons

“…The firing patterns of neurons are heterogeneous in LII 12,29,30,32,34 , and are not less heterogeneous in Cav3.2-expressing neurons. Because of their inactivation properties, T-type calcium channels are first viewed as supporting transient activities 50,62 .…”

“…T-type calcium channels participate in the intrinsic properties of some types of DH neurons 12,29,30,32 . Accordingly, voltage ramps or current-voltage relationships demonstrated the presence of low-voltage and high-voltage activated calcium currents in LII neurons, which could be, respectively, inhibited by NiCl 2 and CdCl 2 (Supplementary Fig.…”

“…The transition from transient behaviors to more regular tonic patterns might be related to the simultaneous decrease in the proportion of rebound-exhibiting neurons and in the decrease in the amplitude of the rebound in the remaining neurons. T-type calcium channels also contribute to tonic firing when they generate a tonic “window” depolarisation 12,13,64,65 . In thalamic neurons, where peak T-type currents are in the nA range, the tonic contribution of T-type channels is ~2mV 36 .…”

“…Pharmacological data support pre- and post-synaptic roles for T-type channels in the dorsal horn (DH) of the spinal cord where primary sensory inputs are first integrated and processed 5–12 . Because of limitations concerning the pharmacology of T-type channels, genetic approaches were required in determining the role of Cav3.2 channels in primary afferent neurons 13–15 .…”

“…This region is well-known to receive descending nociceptive controls to gate sensory flow within the spinal cord, and to undergo disinhibition during allodynia 20–26 . Yet, some unidentified LII interneurons can express T-type channels 14,27 , and can exhibit T-type dependent activity 12,28–32 .…”