Functional differences between 4-aminopyridine and tetraethylammonium-sensitive potassium channels in myelinated axons

Kocsis, Jeffery D.; Eng, Douglas L.; Gordon, Thomas R.; Waxman, Stephen G.

doi:10.1016/0304-3940(87)90296-5

Cited by 74 publications

(40 citation statements)

References 10 publications

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“…Non-inactivating current is important in limiting repetitive firing by holding the membrane potential close to the potassium equilibrium potential. The transient potassium current modulates the repolarization of single action potential, the time required to reach the threshold to fire an action potential, and repetitive firing (Kocsis et al, 1987, Numann et al, 1987, Budde et al, 1992. Our finding that TNF-α only inhibits sustained non-inactivating current suggests that TNF-α-evoked firing or enhancement of spontaneous activity, as reported in our previous study (Liu et al, 2002a, may be caused by regulating the potassium channel at resting membrane potential levels, possibly related to generation of membrane potential oscillations.…”

Section: Discussionsupporting

confidence: 54%

Tumor Necrosis Factor-α Suppresses Sustained Potassium Currents in Rat Small Diameter Sensory Neurons

Liu

Dobretsov²,

Stimers³

et al. 2008

TOPAINJ

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Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, produces pain and hyperalgesia by activating and/or sensitizing nociceptive sensory neurons. In the present study, using whole-cell patch clamp techniques, the regulation of potassium currents by TNF-α was examined in acutely dissociated small dorsal root ganglion neurons. We found that acute application of TNF-α inhibited, in a dose-dependent manner, the non-inactivating sustained potassium current without changing the rapidly inactivating transient current or the kinetics of steady-state inactivation. The effects of TNF-α on potassium currents were similar to that of prostaglandin E2 as reported previously and also demonstrated in the current study. Furthermore, indomethacin, a potent inhibitor for both cyclooxygenase (COX) -1 and COX-2, completely blocked the effect of TNF-α on potassium currents. These results suggest that TNF-α may sensitize or activate sensory neurons by suppressing the sustained potassium current in nociceptive DRG neurons, possibly via stimulating the synthesis/ release of endogenous prostaglandins.

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Section: Discussionsupporting

confidence: 54%

Tumor Necrosis Factor-α Suppresses Sustained Potassium Currents in Rat Small Diameter Sensory Neurons

Liu

Dobretsov²,

Stimers³

et al. 2008

TOPAINJ

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“…Based on their deactivation behaviour in patch-clamp studies, channels with fast (F), intermediate (I), and slow (S) kinetics have been differentiated Safronov et al 1992). Another differentiation of outwardly rectifying axonal K+ channels was made on the basis of pharmacological experiments (Baker et al 1987; Kocsis, Eng, Gordon & Waxman, 1987). Such studies revealed two types of K+ conductances: (a) 4-AP-sensitive channels with fast kinetics of activation and a maximal density in the paranode (Roper & Schwarz, 1989).…”

Section: Different Types Of Axonal K+ Channelsmentioning

confidence: 99%

Hyperglycaemic hypoxia alters after‐potential and fast K+ conductance of rat axons by cytoplasmic acidification.

Schneider¹,

Quasthoff²,

Mitrović³

et al. 1993

The Journal of Physiology

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SUMMARY1. The effects of hyperglyeaemic hypoxia (a condition possibly involved in the pathogenesis of diabetic neuropathy) on the depolarizing after-potential and the potassium conductance of myelinated rat spinal root axons were investigated using electrophysiological recordings from intact spinal roots and from excised, inside-out axonal membrane patches.2. Isolated spinal roots were exposed to hypoxia in solutions containing normal or high glucose concentrations. The depolarizing after-potential of compound action potentials was only enhanced in spinal roots exposed to hyperglycaemic (25 mM Dglucose) hypoxia. A maximal effect was seen in bathing solutions with low buffering power.3. The depolarizing after-potential was also enhanced by cytoplasmic acidification after replacement of 10-30 mm chloride in the bathing solution by propionate.4. Multi-channel current recordings from excised, inside-out axonal membrane patches were used to study the effects of cytoplasmic acidification on voltagedependent K+ conductances with fast (F channels) and intermediate (I channels) kinetics of deactivation.5. F channels were blocked by small changes in cytoplasmic pH (50 % inhibition at pH 6 9). I channels were much less sensitive to intra-axonal acidification.6. In conclusion, our data show that hyperglycaemic hypoxia enhances the depolarizing after-potential in peripheral rat axons. The underlying mechanism seems to be an inhibition of a fast, voltage-dependent axonal K+ conductance by cytoplasmic acidification. This alteration in membrane conductance may contribute to positive symptoms in diabetic neuropathy.

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“…In the myelinated axons of the rat sciatic nerve fibers, 4-AP-sensitive K ϩ channels are related to action potential repolarization, but TEA-sensitive K ϩ channels cause posthyperpolarization after repetitive activity (Kocsis et al, 1987). The application of 4-AP is known to elicit a broad spike of action potentials (Kocsis et al, 1987;Poulter and Padjen, 1995), but such an effect could not be confirmed in this study because we measured extracellular action potentials. In this study, administration of 4-AP at a dose of 2.0 mg/kg increased deflationary SARs during lung deflation at 0 cm of H 2 O.…”

Section: Discussionmentioning

confidence: 75%

“…Both I A (Shaker and Shal) and I K (Shab and Shaw) regulate the timing of action potential formation and the repetitive firing pattern of neuronal cells (Dekin and Getting, 1987;Spigelman et al, 1992). In the myelinated axons of the rat sciatic nerve fibers, 4-AP-sensitive K ϩ channels are related to action potential repolarization, but TEA-sensitive K ϩ channels cause posthyperpolarization after repetitive activity (Kocsis et al, 1987). The application of 4-AP is known to elicit a broad spike of action potentials (Kocsis et al, 1987;Poulter and Padjen, 1995), but such an effect could not be confirmed in this study because we measured extracellular action potentials.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, two broad classes of voltage-gated K ϩ channel currents have been distinguished as to differences in timeand voltage-dependent properties: a typical fast-inactivating A-type current (I A ) and a more sustained K ϩ current of delayed-rectifier type (I K ) (Storm, 1988;Halliwell, 1990). Two pharmacologically different types of K ϩ channels are also identified in the myelinated axons of the rat sciatic nerve fibers: I A is blocked by 4-aminopyridine (4-AP) and I K is blocked by tetraethylammonium (TEA) (Baker et al, 1987;Kocsis et al, 1987). In other series of experiments, the changes in deflationary SAR activity and deflationary SAR AI in response to lung deflation were examined before and after administration of 4-AP or TEA.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Excitatory Mechanism of Deflationary Slowly Adapting Pulmonary Stretch Receptors in the Rat Lung

Matsumoto

Ikeda²,

Nishikawa³

et al. 2002

J Pharmacol Exp Ther

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Functional differences between 4-aminopyridine and tetraethylammonium-sensitive potassium channels in myelinated axons

Cited by 74 publications

References 10 publications

Tumor Necrosis Factor-α Suppresses Sustained Potassium Currents in Rat Small Diameter Sensory Neurons

Tumor Necrosis Factor-α Suppresses Sustained Potassium Currents in Rat Small Diameter Sensory Neurons

Hyperglycaemic hypoxia alters after‐potential and fast K+ conductance of rat axons by cytoplasmic acidification.

Excitatory Mechanism of Deflationary Slowly Adapting Pulmonary Stretch Receptors in the Rat Lung

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