Cell-Specific Alterations of T-Type Calcium Current in Painful Diabetic Neuropathy Enhance Excitability of Sensory Neurons

Jagodic, Miljen M.; Pathirathna, Sriyani; Nelson, Michael T.; Mancuso, Stefani; Joksovic, Pavle M.; Rosenberg, Ethan R; Bayliss, Douglas A.; Jevtović-Todorović, Vesna; Todorović, Slobodan M.

doi:10.1523/jneurosci.4866-06.2007

Cited by 237 publications

(239 citation statements)

References 63 publications

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“…Previous studies demonstrated the existence of T-type Ca 2+ currents in cultured rat DRG neurons [9,28,53]. Under our experimental conditions (10 mM external Ca 2+ ) we could identify cells showing no T-type currents, cells with T-type smaller than HVA currents and cells with Ttype larger than HVA currents.…”

Section: Trpv1 and T-type Channels In Drg Neuronsmentioning

confidence: 49%

“…As T-type channels at the DRG somatic level are known to play a key role in the control of sensory neuron excitability in both physiological conditions [45,66,71] and pain states [28,29], the TRPV1-mediated inhibition of T-type channels reported here has potential overall consequences on nociceptive signals induction and transmission [18,30,31].…”

Section: Trpv1 and T-type Channel Coupling Is Camentioning

confidence: 82%

“…These features are typical of native [8,9] and cloned "low-voltage-activated" T-type channels [17,34,46]. In addition, the pharmacological and kinetic analysis of Ca 2+ currents suggests that the low-voltage-activated Ca 2+ currents are likely carried by the Cav3.2 isoform, the most abundant subtype of T-type channel expressed in rat DRG neurons [5,28,35,55,59]. T-type currents have deactivation kinetics very similar to those reported previously in rat DRG neurons [28,43,60] as well as recombinant rat Cav3.2 Ca 2+ channels [41].…”

Section: Trpv1 and T-type Channels Are Coexpressed In Rat Drg Neuronsmentioning

confidence: 87%

“…In addition, the pharmacological and kinetic analysis of Ca 2+ currents suggests that the low-voltage-activated Ca 2+ currents are likely carried by the Cav3.2 isoform, the most abundant subtype of T-type channel expressed in rat DRG neurons [5,28,35,55,59]. T-type currents have deactivation kinetics very similar to those reported previously in rat DRG neurons [28,43,60] as well as recombinant rat Cav3.2 Ca 2+ channels [41]. These currents are also sensitive to low concentrations of Ni 2+ (50 μM), as reported for DRG neurons and Cav3.2 subunits, while much higher concentrations are required to half-block Cav3.1 (250 μM) and Cav3.3 (216 μM) Ca 2+ channels [36,45].…”

Section: Trpv1 and T-type Channels Are Coexpressed In Rat Drg Neuronsmentioning

confidence: 99%

“…One of the first biophysical characterisations of T-type channels was performed in sensory neurons of dorsal root ganglia (DRG) [7] in which they are highly expressed [20,51]. Increasing evidence indicates that these channels play a key role in modulating sensory neurons excitability, under both normal conditions and pain states [1,28,61,72]. Such studies designated the most abundant isoform of T-type channels expressed in rat DRG neurons (Cav3.2), as a novel pronociceptive channel and, consequently, as a potential therapeutic target for the treatment of acute and chronic pain [5].…”

Section: Introductionmentioning

confidence: 99%

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Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons

Comunanza

Carbone

Marcantoni

et al. 2011

Pflugers Arch - Eur J Physiol

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We studied the inhibitory effects of transient receptor potential vanilloid-1 (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca 2+ channel and highvoltage-activated (HVA; L, N, P/Q, R) currents in rat DRG sensory neurons, as a potential mechanism underlying capsaicin-induced analgesia. T-type and HVA currents were elicited in whole-cell clamped DRG neurons using ramp commands applied before and after 30-s exposures to 1 μM capsaicin. T-type currents were estimated at the first peak of the I-V characteristics and HVA at the second peak, occurring at more positive potentials. Small and medium-sized DRG neurons responded to capsaicin producing transient inward currents of variable amplitudes, mainly carried by Ca 2+. In those cells responding to capsaicin with a large Ca 2+ influx (59% of the total), a marked inhibition of both T-type and HVA Ca 2+ currents was observed. The percentage of T-type and HVA channel inhibition was prevented by replacing Ca 2+ with Ba 2+ during capsaicin application or applying high doses of intracellular BAPTA (20 mM), suggesting that TRPV1-mediated inhibition of T-type and HVA channels is Ca 2+ -dependent and likely confined to membrane nanomicrodomains. Our data are consistent with the idea that TRPV1-induced analgesia may derive from indirect inhibition of both T-type and HVA channels which, in turn, would reduce the threshold of nociceptive signals generation (T-type channel inhibition) and nociceptive synaptic transmission (HVA-channels inhibition).

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Section: Trpv1 and T-type Channels In Drg Neuronsmentioning

confidence: 49%

Section: Trpv1 and T-type Channel Coupling Is Camentioning

confidence: 82%

Section: Trpv1 and T-type Channels Are Coexpressed In Rat Drg Neuronsmentioning

confidence: 87%

Section: Trpv1 and T-type Channels Are Coexpressed In Rat Drg Neuronsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons

Comunanza

Carbone

Marcantoni

et al. 2011

Pflugers Arch - Eur J Physiol

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Voltage‐Gated N‐Type and T‐Type Calcium Channels and Excitability Disorders

Tringham

Snutch

2008

Structure, Function, and Modulation of Neuronal Voltagegated Ion Channels

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INTRODUCTIONCalcium (Ca 2þ ) is a ubiquitous signaling molecule involved in a diverse array of cellular processes ranging from control of membrane excitability to gene transcription, all of which require that intracellular levels be tightly regulated. In particular, voltage-gated Ca 2þ channels (Ca v ) regulate transmembrane fluxes of calcium in response to membrane depolarization. Ca 2þ currents can generally be grouped into two major classes of Ca v channels: high voltage activated (HVA) and low voltage activated (LVA or "T-type"). Based on their pharmacological and biophysical properties, the HVA class can be further subdivided into L-, N-, P/Q-, and R-type channels. The main pore-forming a subunits of the Ca v channels are encoded by 10 different genes, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, and CACNA1S, with a greater variety of subtypes for each class arising from a substantial degree of alternative splicing. Associated with the pore-forming subunit of HVA channels are several accessory subunits, a 2 d (four genes in mammals), b (four genes in mammals), and g (up to eight genes in mammals), although the precise complement is not well determined biochemically for all of the HVA channel types. Further, HVA channel complexity occurs as a result of the

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Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons

Nishizawa

Takahashi

Oguma

et al. 2017

J of Neuroscience Research

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T-type Ca channels and TRPA1 are expressed in sensory neurons and both are associated with pain transmission, but their functional interaction is unclear. Here we demonstrate that pharmacological evidence of the functional relation between T-type Ca channels and TRPA1 in mouse sensory neurons. Low concentration of KCl at 15 mM (15K) evoked increases of intracellular Ca concentration ([Ca ] ), which were suppressed by selective T-type Ca channel blockers. RT-PCR showed that mouse sensory neurons expressed all subtypes of T-type Ca channel. The magnitude of 15K-induced [Ca ] increase was significantly larger in neurons sensitive to allylisothiocyanate (AITC, a TRPA1 agonist) than in those insensitive to it, and in TRPA1 mouse sensory neurons. TRPA1 blockers diminished the [Ca ] responses to 15K in neurons sensitive to AITC, but failed to inhibit 40 mM KCl-induced [Ca ] increases even in AITC-sensitive neurons. TRPV1 blockers did not inhibit the 15K-induced [Ca ] increase regardless of the sensitivity to capsaicin. [Ca ] responses to TRPA1 agonist were enhanced by co-application with 15K. These pharmacological data suggest the possibility of functional interaction between T-type Ca channels and TRPA1 in sensory neurons. Since TRPA1 channel is activated by intracellular Ca , we hypothesize that Ca entered via T-type Ca channel activation may further stimulate TRPA1, resulting in an enhancement of nociceptive signaling. Thus, T-type Ca channel may be a potential target for TRPA1-related pain.

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Cell-Specific Alterations of T-Type Calcium Current in Painful Diabetic Neuropathy Enhance Excitability of Sensory Neurons

Abstract: Recent data indicate that T-type

Cited by 237 publications

References 63 publications

Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons

Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons

Voltage‐Gated N‐Type and T‐Type Calcium Channels and Excitability Disorders

Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons

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Cell-Specific Alterations of T-Type Calcium Current in Painful Diabetic Neuropathy Enhance Excitability of Sensory Neurons

Abstract: Recent data indicate that T-type

Cited by 237 publications

References 63 publications

Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons

Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons

Voltage‐Gated N‐Type and T‐Type Calcium Channels and Excitability Disorders

Possible involvement of transient receptor potential ankyrin 1 in Ca2+ signaling via T‐type Ca2+ channel in mouse sensory neurons

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Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons