Potassium Currents In Sensory Neurons Research Articles

Endothelin-1 raises excitability and reduces potassium currents in sensory neurons

Exposure to endothelin-1 (ET-1, 50 nM) of sensory neurons, acutely isolated from rat dorsal root ganglia (DRG), results in an increase in the number of action potentials elicited by a linear ramp of stimulating current. The changes are complete in 5 min after ET-1 treatment and do not reverse in 5–10 min after ET-1's removal. Neither the resting potential, nor the threshold potential for the first or second action potentials, nor their rate-of-rise or decay, are changed by ET-1 exposure, but the slow depolarizations which occur before the first and second action potentials during the current ramp are increased by ca. 50% by ET-1. The delayed rectifier type of K + currents ( I K), measured under whole-cell voltage clamp, are depressed by ∼30% during such exposure to ET-1. The voltage-dependent gating of steady-state I K and the current kinetics are unchanged by ET-1, leaving the sole effect as a drop in the number of available channels. I K is affected by ET-1 only in Isolectin B 4-positive cells, suggesting that there may be a selective action in enhancing impulse activity on this class of nociceptive neuron. This decrease in I K will potentiate the excitability-inducing actions of the previously reported negative shift in tetrodotoxin-resistant Na + channel gating in such neurons.

Prostaglandin e 2 inhibits the potassium current in sensory neurons from hyperalgesic kv1.1 knockout mice

Prostaglandin E 2 (PGE 2) enhances the sensitivity of sensory neurons to various forms of noxious stimulation. This occurs, in part, by the suppression of a delayed rectifier-like potassium current in these neurons. However, the molecular identity of this current remains unclear. Recent studies demonstrated that a mutant mouse lacking a delayed rectifier potassium channel gene, Kv1.1, displayed lowered thresholds to thermal stimulation in behavioral assays of pain perception, i.e. the Kcna1-null mice were hyperalgesic. Here we examined whether PGE 2 can alter the sensitivity of Kcna1-null mice to noxious stimulation and examine the capability of PGE 2 to inhibit the potassium current in these knockout mice. Behavioral assays were used to assess the effect of PGE 2 on either thermal hyperalgesia or mechanical sensitivities. In addition, the whole-cell patch-clamp technique was used to study the effects of PGE 2 on the total potassium current recorded from isolated mouse sensory neurons. Even with a reduced threshold to thermal stimulation, PGE 2 could still sensitize the response of Kcna1-null mice to thermal and mechanical stimulation by amounts that were similar to that in wild type mice. The activation properties of the potassium current were similar for both the wild type and the Kcna1-null mice, whereas the inactivation properties were different in cells exhibiting large amounts of steady-state inactivation (>50%) measured at +20 mV. PGE 2 suppressed the total potassium current in both groups of mice by 40–50% without altering the voltage dependence of activation. In addition, PGE 2 produced similar amounts of suppression in both groups of mice when currents were examined with the steady-state inactivation protocol. Based on these results, it is unlikely that Kv1.1 is the molecular identity of the potassium channel(s) modulated by PGE 2 to sensitize nociceptive sensory neurons. Also, the enhanced thermal sensitivity as observed in the Kcna1-null mice might be due to more central neurons of the pain sensing pathway.

Analysis of the modulation by serotonin of a voltage-dependent potassium current in sensory neurons of Aplysia

Potassium currents in pleural sensory neurons of Aplysia were studied under control conditions and in the presence of serotonin (5-HT). Using pharmacological techniques we isolated a current that we refer to as IK,V. Although it is not known whether IK,V represents a distinct type of membrane channel, we described its properties using a Hodgkin-Huxley type model. The effects of 5-HT on IK,V were complex. 5-HT decreased by 50% the steady-state magnitude (Iss) of IK,V in response to a voltage-clamp pulse from -50 mV to +20 mV. In addition, 5-HT significantly slowed both activation kinetics (the time constant of activation was increased by 29% at +20 mV) and inactivation kinetics (the time constant of inactivation was increased by 518% at +20 mV). Mathematical descriptions of IK,V in control conditions and in the presence of 5-HT were used to estimate the relative contribution of serotonergic modulation of IK,V to the total 5-HT-induced modulation of membrane currents. Effects of 5-HT on IK,V account for more than 87% of the 5-HT-induced reduction in outward current during the first 20 ms of a voltage-clamp pulse to +20 mV. This result implies that 5-HT exerts many of its effects on spike width in sensory neurons via modulation of IK,V. Effects of 5-HT on IK,V are consistent with a model in which the maximal conductance underlying the current is decreased by 50%, and the rate constants between open and closed states of both the activation and inactivation processes are diminished in magnitude across all membrane potentials.

Potassium currents in chick sensory neurons change with development

We used the whole-cell configuration of the giga-seal voltage-clamp to study voltage-gated potassium currents in sensory neurons dissociated from dorsal root ganglia from embryonic and hatched chicks. Neurons from 8-, 10-, 14-, and 18-day-old embryos (E8, E10, E14, E18) and 1- to 5-day-old chicks were studied under conditions which inhibited inward currents and calcium-activated currents (tetrodotoxin, no added calcium, intracellular EGTA). At all ages, potassium currents were activated by depolarizations to potentials positive to —40 mV. At a given age the amount of inactivation of outward current during 50- to 100-ms steps varied from cell to cell; some cells showed no inactivation while in others the outward current declined to about half of the peak current. On average, the amount of inactivation was fairly stable at E8, E10, E18, and in hatched chicks but showed a transient increase at E14. In contrast, currents clicited by 50-ms test steps following 2-s conditioning steps showed an age dependent change. In E8 neurons, shifting the conditioning voltage from −100 to −90 mV had little or no effect on the current at the end of the test step while earlier outward current was reduced. In cells from older embryos or hatched chicks, similar conditioning voltages caused reductions of both early and late currents during the test step. The relative amount of late current inactivated by this protocol increased as the age of the chicks increased. In addition, the amount of variation in the inactivation properties was larger in cells from older embryos and hatched birds. The changes in outward current occur during a period in which new neurons are formed and existing neurons mature and establish function.