The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity.

Voltage-gated sodium (Na) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal Na channels inhibiting peak current of hNa1.

High-voltage-activated calcium current subtypes in mouse DRG neurons adapt in a subpopulation-specific manner after nerve injury.

Changes in ion channel function and expression are characteristic of neuropathic pain. Voltage-gated calcium channels (VGCCs) are integral for neurotransmission and membrane excitability, but relatively little is known about changes in their expression after nerve injury. In this study, we investigate whether peripheral nerve ligation is followed by changes in the density and proportion of high-voltage-activated (HVA) VGCC current subtypes in dorsal root ganglion (DRG) neurons, the contribution of presynaptic N-type calcium channels in evoked excitatory postsynaptic currents (EPSCs) recorded from dorsal horn neurons in the spinal cord, and the changes in expression of mRNA encoding VGCC subunits in DRG neurons.

MrIC, a novel α-conotoxin agonist in the presence of PNU at endogenous α7 nicotinic acetylcholine receptors.

α-Conotoxins are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Their high selectivity and affinity for the various subtypes of nAChRs have led to significant advances in our understanding of the structure and function of these key ion channels. Here we report the discovery of a novel 4/7 α-conotoxin, MrIC from the venom duct of Conus marmoreus, which acts as an agonist at the endogenous human α7 nAChR in SH-SY5Y cells pretreated with PNU120596 (PNU).

Novel ω-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration.

Background: Antagonists of N-type voltage-gated calcium channels (VGCC), Ca(v)2.2, can manage severe chronic pain with intrathecal use and may be effective systemically. A series of novel ω-conotoxins that selectively inhibit N-type VGCCs was isolated from Conus catus.

Opioid-related (ORL1) receptors are enriched in a subpopulation of sensory neurons and prolonged activation produces no functional loss of surface N-type calcium channels.

The opioid-related receptor, ORL1, is activated by the neuropeptide nociceptin/orphanin FQ (N/OFQ) and inhibits high-voltage-activated (HVA) calcium channel currents (I(Ca)) via a G-protein-coupled mechanism. Endocytosis of ORL1 receptor during prolonged N/OFQ exposure was proposed to cause N-type voltage-gated calcium channel (VGCC) internalization via physical interaction between ORL1 and the N-type channel. However, there is no direct electrophysiological evidence for this mechanism in dorsal root ganglion (DRG) neurons or their central nerve terminals.