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

Jing Wu,Linghui Xiao,Changyu Jiang,Daying Zhang,Haixia Kuang,Xiaoe Cheng,Tao Liu,Sicong Peng,Mengye Zhu

doi:10.3389/fncel.2018.00370

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.

Highlights

T-type calcium channels are low-voltage activated (LVA) calcium channels, consisting of three isoforms: Cav3.1, Cav3.2 and Cav3.3 (Bourinet et al, 2016)
Net T-type currents were obtained by digital subtraction of the inward currents in the absence and presence of NiCl2 (Figure 1Ad)
The current density, which was calculated by dividing the peak amplitude of T-type current by the cell capacitance, was not significantly different among those recorded in the conditions of control, TTX and digital subtraction of NiCl2 (p > 0.05; n = 19 cells in four rats; Figure 1B)

Summary

Introduction

T-type calcium channels are low-voltage activated (LVA) calcium channels, consisting of three isoforms: Cav3.1, Cav3.2 and Cav3.3 (Bourinet et al, 2016). They are broadly distributed in vertebrates, including the central and peripheral nervous system, heart, smooth muscle and so on Iftinca (2011). T-type channels have been implicated in the modulation of neuronal excitability, they are linked to the pathogenesis of various neurological disorders, including epilepsy, autism and chronic pain (Zamponi, 2016). Abundant expression of T-type channels has been found in pain-processing pathways, including dorsal root ganglion (DRG) and superficial spinal dorsal horn (SDH; François et al, 2015). Blockade of T-type channels has been proved to be efficient for pain relief (Garcia-Caballero et al, 2014; Snutch and Zamponi, 2017)

Methods

Results

Conclusion