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5-HT modulation of hyperpolarization-activated inward current and calcium- dependent outward current in a crustacean motor neuron

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1. Serotonergic modulation of a hyperpolarization-activated inward current, I(h), and a calcium-dependent outward current, I(o(Ca)), was examined in the dorsal gastric (DG) motor neuron, with the use of intracellular recording techniques in an isolated preparation of the crab stomatogastric ganglion (STG). 2. Hyperpolarization of the membrane from rest with maintained current pulses resulted in a slow time-dependent relaxation back toward rest and a depolarizing overshoot after termination of the current pulse. In voltage clamp, hyperpolarizing commands negative to approximately -70 mV caused a slowly developing inward current, I(h), which showed no inactivation. Repolarization back to the holding potential of -50 mV revealed a slow inward tail current. 3. The reversal potential for I(h) was approximately -35 mV. Raising extracellular K+ concentration ([K+](o)) from 11 to 22 mM enhanced, whereas decreasing extracellular Na+ concentration ([Na+](o)) reduced the amplitude of I(h). These results indicate that I(h) in DG is carried by both K+ and Na+ ions. 4. Bath application of serotonin (5-HT; 10 μM) caused a marked increase in the amplitude of I(h) through its active voltage ranges. 5. The time course of activation of I(h) was well fitted by a single exponential function and strongly voltage dependent. 5-HT increased the rate of activation of I(h). 5- HT also slowed the rate of deactivation of the I(h) tail on repolarization to -50 mV. 6. The activation curve for the conductance (G(h)) underlying I(h) was obtained by analyzing tail currents. 5-HT shifted the half activation for G(h) from approximately -105 mV in control to -95 mV, resulting in an increase in the amplitude of G(h) active at rest. 7. Two to 4 mM Cs+ abolished I(h), whereas barium (200 μM to 2 mM) had only weak suppressing effects on I(h). Concomitantly, Cs+ also blocked the 5-HT-induced inward current and conductance increase seen at voltages negative to rest. In current clamp, Cs+ caused DG to hyperpolarize 3-4 mV from rest, suggesting that I(h) is partially active at rest and contributes to the resting membrane potential. 8. Depolarizing voltage commands from a holding potential of -50 mV resulted in a total outward current (I(o)) with an initial transient component and a sustained steady-state component. Application of 5-HT reduced both the transient and sustained components of I(o). 9. I(o) was reduced by 10-20 mM tetraethylammonium (TEA), suggesting that it is primarily a K+ current. TEA abolished the response to 5-HT in the depolarizing range, suggesting that 5-HT acts by reducing an outward potassium current. 10. Low extracellular calcium reduced the same components of I(o) as did 5-HT. Low extracellular calcium also reduced or eliminated the 5-HT response in the depolarizing range, suggesting that 5-HT specifically reduces I(o(Ca)). 11. These results demonstrate that 5-HT has dual effects on the DG motor neuron, in the crab stomatogastric ganglion. We suggest that changes in the two conductances are responsible for the mixed conductance increase and decrease described in an accompanying paper in response to stimulation of peripheral serotonergic stretch receptor cells and local 5-HT application. These conductance changes are at least partially responsible for the serotonergic induction of plateau properties in DG.

TidsskriftJournal of Neurophysiology
Udgave nummer2
Sider (fra-til)496-508
Antal sider13
StatusUdgivet - 1 jan. 1992

ID: 194980091