Lidocaine Inhibits HCN Currents in Rat Spinal Substantia Gelatinosa Neurons

Hu, Tao; Liu, Nana; Lv, Minhua; Ma, Long‐Xian; Peng, Huizhen; Peng, Sicong; Liu, Tao

doi:10.1213/ane.0000000000001140

Cited by 17 publications

(13 citation statements)

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“…Averaged spike frequencies vs. the hyperpolarizing pre-pulses were shown in the right panel ( n = 13 cells in nine rats). Meanwhile, we found that the mean latency to peak of the rebound depolarization was 69.6 ± 19.3 ms at −120 pA. Our previous study has shown that SG neurons exhibit various firing patterns, encompassing tonic firing, delayed firing, single spike, initial burst, phasic firing, gap firing and reluctant firing (Hu et al, 2016 ). Exemplars of tonic firing at different depolarized membrane potentials were shown in Figure 5C .…”

Section: Resultsmentioning

confidence: 64%

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

Peng

Xiao

et al. 2018

Front. Cell. Neurosci.

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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.

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Section: Resultsmentioning

confidence: 64%

“…Spinal cord slices were prepared as our previous studies (Liu et al, 2015 ; Hu et al, 2016 ). Briefly, animals were deeply anesthetized with urethane (1.5 g/kg, i.p.)…”

Section: Methodsmentioning

confidence: 99%

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

Peng

Xiao

et al. 2018

Front. Cell. Neurosci.

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“…In contrast, the expression of HCN3 and HCN4 in the CNS appears less abundant. Interestingly, I h currents have also been reported in reactive brain astrocytes as well as pain-processing neurons in the spinal cord [90][91][92]. Interestingly, I h currents have also been reported in reactive brain astrocytes as well as pain-processing neurons in the spinal cord [90][91][92].…”

Section: Decreased Neuronal Activitymentioning

confidence: 97%

HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain

Tsantoulas

Mooney

McNaughton

2016

Biochemical Journal

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Nociception - the ability to detect painful stimuli - is an invaluable sense that warns against present or imminent damage. In patients with chronic pain, however, this warning signal persists in the absence of any genuine threat and affects all aspects of everyday life. Neuropathic pain, a form of chronic pain caused by damage to sensory nerves themselves, is dishearteningly refractory to drugs that may work in other types of pain and is a major unmet medical need begging for novel analgesics. Hyperpolarisation-activated cyclic nucleotide (HCN)-modulated ion channels are best known for their fundamental pacemaker role in the heart; here, we review data demonstrating that the HCN2 isoform acts in an analogous way as a 'pacemaker for pain', in that its activity in nociceptive neurons is critical for the maintenance of electrical activity and for the sensation of chronic pain in pathological pain states. Pharmacological block or genetic deletion of HCN2 in sensory neurons provides robust pain relief in a variety of animal models of inflammatory and neuropathic pain, without any effect on normal sensation of acute pain. We discuss the implications of these findings for our understanding of neuropathic pain pathogenesis, and we outline possible future opportunities for the development of efficacious and safe pharmacotherapies in a range of chronic pain syndromes.

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“…The reversal potential of I h current (i.e., the x-intercept of the current-voltage curve, which can be represented as V rev ) was also shifted toward hyperpolarized voltages. Such an effect is believed to correspond to the altered ion selectivity of HCN channels (Hu et al, 2016). However, the shift in the V rev of I h current could be also attributed to the effect of leak currents.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (I_h) in hippocampal CA1 neurons in a rat model of traumatic brain injury

et al. 2020

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Traumatic brain injury (TBI) is associated with epileptiform activity in the hippocampus; however, the underlying mechanisms have not been fully determined. The goal was to understand what changes take place in intrinsic neuronal physiology in the hippocampus after blunt force trauma to the cortex. In this context, hyperpolarization-activated cation current (I h) currents may have a critical role in modulating the neuronal intrinsic membrane excitability; therefore, its contribution to the TBI-induced hyperexcitability was assessed. In a model of TBI caused by controlled cortical impact (CCI), the intrinsic electrophysiological properties of pyramidal neurons were examined 1 week after TBI induction in rats. Whole-cell patch-clamp recordings were performed under current-and voltage-clamp conditions following ionotropic receptors blockade. Induction of TBI caused changes in the intrinsic excitability of pyramidal neurons, as shown by a significant increase and decrease in firing frequency and in the rheobase current, respectively (p < .05). The evoked firing rate and the action potential time to peak were also significantly increased and decreased, respectively (p < .05). In the TBI group, the amplitude of instantaneous and steadystate I h currents was both significantly smaller than those in the control group (p < .05). The I h current density was also significantly decreased (p < .001). Findings indicated that TBI led to an increase in the intrinsic excitability in CA1 pyramidal neurons and changes in I h current could be, in part, one of the underlying mechanisms involved in this hyperexcitability.

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Lidocaine Inhibits HCN Currents in Rat Spinal Substantia Gelatinosa Neurons

Abstract: Published ahead of print January 11, 2016

Cited by 17 publications

References 58 publications

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

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

HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain

Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (I_h) in hippocampal CA1 neurons in a rat model of traumatic brain injury

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Lidocaine Inhibits HCN Currents in Rat Spinal Substantia Gelatinosa Neurons

Abstract: Published ahead of print January 11, 2016

Cited by 17 publications

References 58 publications

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

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

HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain

Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (Ih) in hippocampal CA1 neurons in a rat model of traumatic brain injury

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Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (I_h) in hippocampal CA1 neurons in a rat model of traumatic brain injury