scholarly journals Serotonin modulates multiple calcium current subtypes in commissural interneurons of the neonatal mouse

2012 ◽  
Vol 107 (8) ◽  
pp. 2212-2219 ◽  
Author(s):  
Matthew D. Abbinanti ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Spinal Cord ◽  
Voltage Clamp ◽  
Calcium Current ◽  
Potassium Current ◽  
Cell Voltage ◽  
Pattern Generator ◽  
Calcium Currents ◽  
Intrinsic Properties ◽  
Mouse Spinal Cord ◽  
Serotonergic Modulation

Calcium currents are critical to the intrinsic properties of neurons and the networks that contain them. These currents make attractive targets for neuromodulation. Here, we examine the serotonergic modulation of specific calcium current subtypes in neonatal (P0-5) intersegmental commissural interneurons (CINs), members of the hindlimb locomotor central pattern generator in the mouse spinal cord. Previous work in our lab showed that serotonin (5-HT) excited CINs in part by reducing a calcium current and thus indirectly reducing the calcium-activated potassium current ( Diaz-Rios et al. 2007 ). We have determined which calcium currents are targets of serotonin modulation. Utilizing whole cell voltage clamp and toxins to specific calcium current subtypes, we found that N- and P/Q-type currents comprise over 60% of the overall calcium current. Blockade of each of these subtypes alone with either ω-conotoxin GVIA or ω-agatoxin TK was unable to occlude 5-HT's reduction of the calcium current. However, coapplication of both blockers together fully occluded 5-HT's reduction of the calcium current. Thus, 5-HT decreases both N- and P/Q-type calcium current to excite neonatal CINs.

scholarly journals Postnatal emergence of serotonin-induced plateau potentials in commissural interneurons of the mouse spinal cord

2012 ◽  
Vol 108 (8) ◽  
pp. 2191-2202 ◽  
Author(s):  
Matthew D. Abbinanti ◽  
Guisheng Zhong ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Calcium Current ◽  
Potassium Current ◽  
Neonatal Period ◽  
Calcium Currents ◽  
Intrinsic Properties ◽  
Developmental Difference ◽  
Plateau Potentials ◽  
Plateau Potential ◽  
Voltage Clamp Analysis ◽  
Serotonergic Modulation

Most studies of the mouse hindlimb locomotor network have used neonatal (P0–5) mice. In this study, we examine the postnatal development of intrinsic properties and serotonergic modulation of intersegmental commissural interneurons (CINs) from the neonatal period (P0–3) to the time the animals bear weight (P8–10) and begin to show adult walking (P14–16). CINs show an increase in excitability with age, associated with a decrease in action potential halfwidth and appearance of a fast component to the afterhyperpolarization at P14–16. Serotonin (5-HT) depolarizes and increases the excitability of most CINs at all ages. The major developmental difference is that serotonin can induce plateau potential capability in P14–16 CINs, but not at younger ages. These plateau potentials are abolished by nifedipine, suggesting that they are mediated by an L-type calcium current, ICa(L). Voltage-clamp analysis demonstrates that 5-HT increases a nifedipine-sensitive voltage-activated calcium current, ICa(V), in P14–16 CINs but does not increase ICa(V) in P8–10 CINs. These results, together with earlier work on 5-HT effects on neonatal CINs, suggest that 5-HT increases the excitability of CINs at all ages studied, but by opposite effects on calcium currents, decreasing N- and P/Q-type calcium currents and, indirectly, calcium-activated potassium current, at P0–3 but increasing ICa(L) at P14–16.

GABAB receptor activation causes a depression of low- and high-voltage-activated Ca2+ currents, postinhibitory rebound, and postspike afterhyperpolarization in lamprey neurons

1993 ◽  
Vol 70 (6) ◽  
pp. 2606-2619 ◽  
Author(s):  
T. Matsushima ◽  
J. Tegner ◽  
R. H. Hill ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Voltage Clamp ◽  
Calcium Current ◽  
Gabab Receptor ◽  
Receptor Activation ◽  
Calcium Currents ◽  
Gabab Receptors ◽  
Peak Amplitude ◽  
Duration Of Action

1. Activation of gamma-aminobutyric acid-B (GABAB) receptors during N-methyl-D-aspartate (NMDA)-induced fictive locomotor activity in the lamprey spinal cord reduces the burst frequency and changes the intersegmental coordination. Presynaptic inhibition of both the excitatory and inhibitory synaptic transmission from spinal premotor interneurons occurs through GABAB receptor activation. To further analyze the cellular mechanisms underlying the GABABergic modulation of the locomotor network, the present study investigates somatodendritic effects of GABAB receptor activation on interneurons and motoneurons in the lamprey spinal cord in vitro using single-electrode current- and voltage-clamp techniques. 2. High- (HVA) and low- (LVA) voltage-activated calcium currents were studied with single-electrode voltage clamp when Na+ and K+ currents were blocked--using tetrodotoxin, tetraethylammonium (TEA), and CsCl electrodes--after substituting Ca2+ with Ba2+. Cobalt-sensitive inward barium currents, activated at -50 mV, became larger when the holding potential was set to a more hyperpolarized level, thus suggesting the existence of an LVA calcium current. The presence of cobalt-sensitive inward barium currents activated at -30 and -10 mV suggests the existence of an HVA calcium current. GABAB receptor activation (baclofen) reduced the peak amplitude of both the LVA and HVA Ca2+ component. 3. The late phase of the afterhyperpolarization (AHP), which follows the action potential, was reduced in amplitude by cobalt, thus lending further support to the notion that the Ca2+ influx, and the subsequent activation of Ca(2+)-dependent K+ channels (KCa2+), constitutes the major part of the AHP generation. Application of the GABAB agonist baclofen also reduced the peak amplitude of the AHP in interneurons and motoneurons, and this reduction was counteracted by the GABAB antagonist 2(OH)saclofen. Baclofen reduced the duration of action potentials broadened by TEA, thus suggesting that the Ca2+ inflow was reduced. Intracellular injection of the GTP analogue GTP gamma S also reduced the duration of the action potential and the peak amplitude of the AHP in TEA, thus supporting the notion that a GTP-binding protein (G-protein)-mediated GABAB receptor activation reduced the calcium inflow, leading to less activation of KCa channels and, consequently, to a smaller peak amplitude of the AHP. 4. Baclofen suppressed the subthreshold depolarization induced by a depolarizing current pulse injection without affecting either the spike threshold or the resting membrane conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholecystokinin-gated currents in neurons of the rat solitary complex in vitro

1993 ◽  
Vol 70 (6) ◽  
pp. 2584-2595 ◽  
Author(s):  
P. Branchereau ◽  
J. Champagnat ◽  
M. Denavit-Saubie
Keyword(s):  
Voltage Clamp ◽  
Potassium Current ◽  
Reversal Potential ◽  
Input Resistance ◽  
Calcium Currents ◽  
Equilibrium Potential ◽  
Potassium Ions ◽  
Nernst Equation ◽  
Membrane Hyperpolarization ◽  
Cckb Receptor

1. Ionic conductances controlled by type A and type B cholecystokinin (CCK) receptors were studied in neurons of the rat nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMNV), using intracellular and whole-cell patch clamp recordings in current or voltage clamp configuration during bath application of agonists (CCK8, CCK4, BC 264) and antagonists. 2. CCKA receptor-related inhibition was associated with a membrane hyperpolarization and a decrease in input resistance that developed 2-6 min after the arrival of drug into the extracellular medium. These effects were induced by 5 nM CCK8 but not BC 264 and they were blocked by the CCKA antagonist, L-364,718, but not by the CCKB antagonist, L-365,260. 3. CCKA receptor-related inhibition was generated by a potassium current that reversed at a reversal potential E(rev) of -73 +/- 1 (mean +/- SE) mV with bathing potassium concentration [K+]o = 6 mM and at -88 +/- 1 with [K+]o = 3 mM, in agreement with the Nernst equation for potassium ions. 4. CCKB receptor-related excitation was associated with a membrane depolarization and an increase of the input resistance induced by the following agonists at threshold concentrations: CCK8 (0.2 nM) > or = BC 264 (0.4 nM) > CCK4 (10.9 nM). The increase of input resistance was abolished by L-365,260 and was maintained after blockade of the CCKA current by L-364,718. 5. CCKB receptor-related excitation, in the neurons (30% of cases) in which clear response reversal was observed, appeared to be generated by a decrease of a potassium conductance. Responses showed a reversal potential E(rev) of -68 +/- 4 mV with [K+]o = 6 mM and -89 +/- 1 mV with [K+]o = 3 mM, verifying predictions from the Nernst equation applied to potassium ions. However, in 70% of cases, clear reversal was not observed at membrane potentials negative to the theoretical potassium equilibrium potential EK. 6. In voltage clamp studies, CCK8 induced a 181 +/- 17 pA inward current associated with a 26 +/- 4% decrease in the instantaneous current (I(ins)) generated by hyperpolarizing voltage steps. This effect on I(ins) was demonstrated in the absence of effects on the outward noninactivating potassium current (IM) and on the inward noninactivating cationic current (IQ). 7. CCKB receptor-mediated excitation was not suppressed by cobalt, a blocker of calcium currents, and was not associated with a change of the calcium-dependent potassium current (IK(Ca)).(ABSTRACT TRUNCATED AT 400 WORDS)

Serotonin Modulates Dendritic Calcium Influx in Commissural Interneurons in the Mouse Spinal Locomotor Network

2007 ◽  
Vol 98 (4) ◽  
pp. 2157-2167 ◽  
Author(s):  
Manuel Díaz-Ríos ◽  
Daniel A. Dombeck ◽  
Watt W. Webb ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Spinal Cord ◽  
Voltage Clamp ◽  
Neuronal Excitability ◽  
Calcium Influx ◽  
Active Role ◽  
Calcium Currents ◽  
Detectable Effect ◽  
Lumbar Region ◽  
Fictive Locomotion ◽  
Voltage Dependent

Commissural interneurons (CINs) help to coordinate left–right alternating bursting activity during fictive locomotion in the neonatal mouse spinal cord. Serotonin (5-HT) plays an active role in the induction of fictive locomotion in the isolated spinal cord, but the cellular targets and mechanisms of its actions are relatively unknown. We investigated the possible role of serotonin in modifying dendritic calcium currents, using a combination of two-photon microscopy and patch-clamp recordings, in identified CINs in the upper lumbar region. Dendritic calcium responses to applied somatic voltage-clamp steps were measured using fluorescent calcium indicator imaging. Serotonin evoked significant reductions in voltage-dependent dendritic calcium influx in about 40% of the dendritic sites studied, with no detectable effect in the remaining sites. We also detected differential effects of serotonin in different dendritic sites of the same neuron; serotonin could decrease voltage-sensitive calcium influx at one site, with no effect at a nearby site. Voltage-clamp studies confirmed that serotonin reduces the voltage-dependent calcium current in CINs. Current-clamp experiments showed that the serotonin-evoked decreases in dendritic calcium influx were coupled with increases in neuronal excitability; we discuss possible mechanisms by which these two seemingly opposing results can be reconciled. This research demonstrates that dendritic calcium currents are targets of serotonin modulation in a group of spinal interneurons that are components of the mouse locomotor network.

Oxytocin actions on voltage-dependent ionic channels in pregnant rat uterine smooth muscle cells

1992 ◽  
Vol 70 (12) ◽  
pp. 1597-1603 ◽  
Author(s):  
Yoshihito Inoue ◽  
Keiichi Shimamura ◽  
Nicholas Sperelakis
Keyword(s):  
Smooth Muscle ◽  
Voltage Clamp ◽  
Calcium Current ◽  
Uterine Contraction ◽  
Cell Voltage ◽  
Ionic Channels ◽  
Pregnant Rat ◽  
Uterine Smooth Muscle ◽  
Voltage Dependent ◽  
Sodium And Potassium

The effects of oxytocin, a uterotonic polypeptide hormone, on the voltage-dependent slow calcium, fast sodium, and potassium channel currents were studied using whole-cell voltage clamp of freshly isolated cells from late pregnant (18–21 day) rat myometrium. The calcium current was rapidly inhibited by oxytocin (about 25% inhibition at 20 nM) in a dose-dependent manner, and this inhibitory effect was completely reversible by washout. However, inhibition was not observed when barium was used as the charge carrier. Sodium current and potassium current were not modified by oxytocin, thus sodium and potassium currents may not play important roles in oxytocin-induced augmentation of uterine contraction. It is concluded that oxytocin stimulates uterine contraction by mechanisms other than augmentation of the voltage-dependent calcium current, e.g., by release of Ca from sarcoplasmic reticulum (by inositol trisphosphate) or by activation of a receptor-operated Ca channel. The inhibition of the slow calcium current may be induced by the elevation of [Ca]i.Key words: oxytocin, ionic channels, uterine smooth muscle, whole-cell voltage clamp, pregnant rat myometrium.

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