Ionic mechanisms maintaining action potential conduction velocity at high firing frequencies in an unmyelinated axon

Abstract

The descending contralateral movement detector (DCMD) is a high‐performance interneuron in locusts with an axon capable of transmitting action potentials (AP) at more than 500 Hz. We investigated biophysical mechanisms for fidelity of high‐frequency transmission in this axon. We measured conduction velocities (CVs) at room temperature during exposure to 10 mmol/L cadmium, a calcium current antagonist, and found significant reduction in CV with reduction at frequencies >200 Hz of ~10%. Higher temperatures induced greater CV reductions during exposure to cadmium across all frequencies of ~20–30%. Intracellular recordings during 15 min of exposure to cadmium or nickel, also a calcium current antagonist, revealed an increase in the magnitude of the afterhyperpolarization potential (AHP) and the time to recover to baseline after the AHP (Medians for Control: −19.8%; Nickel: 167.2%; Cadmium: 387.2%), that could be due to a T‐type calcium current. However, the removal of extracellular calcium did not mimic divalent cation exposure suggesting calcium currents are not the cause of the AHP increase. Computational modeling showed that the effects of the divalent cations could be modeled with a persistent sodium current which could be blocked by high concentrations of divalent cations. Persistent sodium current shortened the AHP duration in our models and increased CV for high‐frequency APs. We suggest that faithful, high‐frequency axonal conduction in the DCMD is enabled by a mechanism that shortens the AHP duration like a persistent or resurgent sodium current.

Model of Impedance Changes in Unmyelinated Nerve Fibers

“…These models steadily improved the accuracy of simulation of the action potentials' shape, excitability thresholds' temporal behaviour and its different complex features like activity-dependent slowing (ADS) and recovery cycles. For example, Scriven simulated repetitive firing phenomena by modelling the Na-K pump, finite intra-axonal and periaxonal volumes and calcium ion channels [25]; Herzog and colleagues first included TTX resistant sodium channels (now called Nav1.9) in a model of DRG neurons [26]; Tigerholm together with his group were able to model activity-dependent slowing and recovery cycles for C-nociceptors [27]; Cross and Robertson studied ionic mechanisms accompanying high-frequency firing of the descending contralateral movement detector (DCMD) axons [28]. Numerous other neural models have been developed in recent years, including for myelinated fibres [29], [30] and for groups of fibres [31]- [33].…”

Inhibition of Voltage-Gated Na+ Currents Exerted by KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea), an Inhibitor of Na+-Ca2+ Exchanging Process

“…Alternatively, in addition to being activated by depolarizing voltage pulses rather than by repolarizing voltage steps, I Na(R) was found to activate and decay more slowly than I Na(T) [ 55 ]. As a result, I Na(R) has been thought to help produce rapid depolarization immediately following an action potential; hence, it is suited either for cells that fire spontaneously at a higher firing rate, or to offer noise modulation in neurons with varying bursting firing [ 52 , 54 , 56 ]. In this regard, efforts were additionally made to see if the presence of KB-R7943 could exert any perturbations on such an instantaneous current evoked by the descending V ramp .…”

“…Previous reports have shown that the extent of I Na(W) ’s strength is linked to the magnitude of background or residual steady Na + currents in many excitable cells [ 47 , 48 , 50 , 71 ]. Meanwhile, I Na(R) ’s magnitude has also been demonstrated to be associated with high-frequency or varying burst firing of action potentials in excitable cells (e.g., cerebellar Purkinje neurons) [ 51 , 52 , 53 , 54 , 55 , 56 , 72 ]. Moreover, the I Na(P) magnitude induced by sinusoidal voltage waveform was also augmented by adding Tef; of note, the further addition of KB-R7943 could attenuate Tef-augmented I Na(P) .…”

Yüksek fruktoz diyeti ile beslenen sıçanlarda artmış kan glukozuna neuromedin U yanıtının araştırılması

“…Bu durum sıçanlara verilen anestezinin etkisinden ortaya çıkmış olabilir. Anesteziklerin kan şekeri regülasyonunu bozduğu ve anestezi altındaki deney hayvanın yüksek kan glikoz değerlerine sahip olduğu literatürde gösterildi [25]. Açlık kan insülin düzeyindeki kalıbı HOMA-IR skorunda da gözledik.…”