KChIP1 and Frequenin Modify shal-Evoked Potassium Currents in Pyloric Neurons in the Lobster Stomatogastric Ganglion

2003 ◽  
Vol 89 (4) ◽  
pp. 1902-1909 ◽  
Author(s):  
Y. Zhang ◽  
J. N. MacLean ◽  
W. F. An ◽  
C. C. Lanning ◽  
R. M. Harris-Warrick
Keyword(s):  
Potassium Current ◽  
Time Course ◽  
Spiny Lobster ◽  
Stomatogastric Ganglion ◽  
K Channel ◽  
Panulirus Interruptus ◽  
Recovery From Inactivation ◽  
Pyloric Dilator ◽  
Ef Hand ◽  
Firing Properties

The transient potassium current ( I A) plays an important role in shaping the firing properties of pyloric neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. The shal gene encodes I A in pyloric neurons. However, when we over-expressed the lobster Shal protein by shal RNA injection into the pyloric dilator (PD) neuron, the increased I A had somewhat different properties from the endogenous I A. The recently cloned K-channel interacting proteins (KChIPs) can modify vertebrate Kv4 channels in cloned cell lines. When we co-expressed hKChIP1 with lobster shal in Xenopusoocytes or lobster PD neurons, they produced A-currents resembling the endogenous I A in PD neurons; compared with currents evoked by shal alone, their voltage for half inactivation was depolarized, their kinetics of inactivation were slowed, and their recovery from inactivation was accelerated. We also co-expressed shal in PD neurons with lobster frequenin, which encodes a protein belonging to the same EF-hand family of Ca2+ sensing proteins as hKChIP. Frequenin also restored most of properties of the shal-evoked currents to those of the endogenous A-currents, but the time course of recovery from inactivation was not corrected. These results suggest that lobster shal proteins normally interact with proteins in the KChIP/frequenin family to produce the transient potassium current in pyloric neurons.

scholarly journals Correlation between Charge Movement and Ionic Current during Slow Inactivation in Shaker K+ Channels

1997 ◽  
Vol 110 (5) ◽  
pp. 579-589 ◽  
Author(s):  
Riccardo Olcese ◽  
Ramón Latorre ◽  
Ligia Toro ◽  
Francisco Bezanilla ◽  
Enrico Stefani
Keyword(s):  
Time Course ◽  
Voltage Dependence ◽  
Ionic Current ◽  
K Channel ◽  
Charge Movement ◽  
Slow Inactivation ◽  
Gating Currents ◽  
Similar Time ◽  
K Channels ◽  
Recovery From Inactivation

Prolonged depolarization induces a slow inactivation process in some K+ channels. We have studied ionic and gating currents during long depolarizations in the mutant Shaker H4-Δ(6–46) K+ channel and in the nonconducting mutant (Shaker H4-Δ(6–46)-W434F). These channels lack the amino terminus that confers the fast (N-type) inactivation (Hoshi, T., W.N. Zagotta, and R.W. Aldrich. 1991. Neuron. 7:547–556). Channels were expressed in oocytes and currents were measured with the cut-open-oocyte and patch-clamp techniques. In both clones, the curves describing the voltage dependence of the charge movement were shifted toward more negative potentials when the holding potential was maintained at depolarized potentials. The evidences that this new voltage dependence of the charge movement in the depolarized condition is associated with the process of slow inactivation are the following: (a) the installation of both the slow inactivation of the ionic current and the inactivation of the charge in response to a sustained 1-min depolarization to 0 mV followed the same time course; and (b) the recovery from inactivation of both ionic and gating currents (induced by repolarizations to −90 mV after a 1-min inactivating pulse at 0 mV) also followed a similar time course. Although prolonged depolarizations induce inactivation of the majority of the channels, a small fraction remains non–slow inactivated. The voltage dependence of this fraction of channels remained unaltered, suggesting that their activation pathway was unmodified by prolonged depolarization. The data could be fitted to a sequential model for Shaker K+ channels (Bezanilla, F., E. Perozo, and E. Stefani. 1994. Biophys. J. 66:1011–1021), with the addition of a series of parallel nonconducting (inactivated) states that become populated during prolonged depolarization. The data suggest that prolonged depolarization modifies the conformation of the voltage sensor and that this change can be associated with the process of slow inactivation.

scholarly journals Inactivation Gating of Kv4 Potassium Channels

1999 ◽  
Vol 113 (5) ◽  
pp. 641-660 ◽  
Author(s):  
Henry H. Jerng ◽  
Mohammad Shahidullah ◽  
Manuel Covarrubias
Keyword(s):  
Time Course ◽  
Membrane Potentials ◽  
Structural Basis ◽  
K Channel ◽  
Inactivation Curve ◽  
Double Mutation ◽  
K Channels ◽  
Closed State ◽  
Recovery From Inactivation ◽  
Inactivation Gating

Kv4 channels represent the main class of brain A-type K+ channels that operate in the subthreshold range of membrane potentials (Serodio, P., E. Vega-Saenz de Miera, and B. Rudy. 1996. J. Neurophysiol. 75:2174– 2179), and their function depends critically on inactivation gating. A previous study suggested that the cytoplasmic NH2- and COOH-terminal domains of Kv4.1 channels act in concert to determine the fast phase of the complex time course of macroscopic inactivation (Jerng, H.H., and M. Covarrubias. 1997. Biophys. J. 72:163–174). To investigate the structural basis of slow inactivation gating of these channels, we examined internal residues that may affect the mutually exclusive relationship between inactivation and closed-state blockade by 4-aminopyridine (4-AP) (Campbell, D.L., Y. Qu, R.L. Rasmussen, and H.C. Strauss. 1993. J. Gen. Physiol. 101:603–626; Shieh, C.-C., and G.E. Kirsch. 1994. Biophys. J. 67:2316–2325). A double mutation V[404,406]I in the distal section of the S6 region of the protein drastically slowed channel inactivation and deactivation, and significantly reduced the blockade by 4-AP. In addition, recovery from inactivation was slightly faster, but the pore properties were not significantly affected. Consistent with a more stable open state and disrupted closed state inactivation, V[404,406]I also caused hyperpolarizing and depolarizing shifts of the peak conductance–voltage curve (∼5 mV) and the prepulse inactivation curve (>10 mV), respectively. By contrast, the analogous mutations (V[556,558]I) in a K+ channel that undergoes N- and C-type inactivation (Kv1.4) did not affect macroscopic inactivation but dramatically slowed deactivation and recovery from inactivation, and eliminated open-channel blockade by 4-AP. Mutation of a Kv4-specifc residue in the S4–S5 loop (C322S) of Kv4.1 also altered gating and 4-AP sensitivity in a manner that closely resembles the effects of V[404,406]I. However, this mutant did not exhibit disrupted closed state inactivation. A kinetic model that assumes coupling between channel closing and inactivation at depolarized membrane potentials accounts for the results. We propose that components of the pore's internal vestibule control both closing and inactivation in Kv4 K+ channels.

Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito

2004 ◽  
Vol 286 (2) ◽  
pp. H602-H609 ◽  
Author(s):  
Fadi G. Akar ◽  
Richard C. Wu ◽  
Isabelle Deschenes ◽  
Antonis A. Armoundas ◽  
Valentino Piacentino ◽  
...  
Keyword(s):  
Time Course ◽  
Ventricular Myocytes ◽  
Phenotypic Expression ◽  
Functional Expression ◽  
K Channel ◽  
Inactivation Kinetics ◽  
Phenotypic Properties ◽  
Interacting Protein ◽  
Phenotypic Differences ◽  
Recovery From Inactivation

The Ca2+-independent transient outward K+ current ( Ito) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of Ito. To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular Ito of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine Ito. Whereas recovery from inactivation of human Ito followed a monoexponential time course, canine Ito recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine Ito, and exposure to oxidative stress did not alter the inactivation kinetics of Ito in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kv1.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular Ito despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of Ito between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode Ito, but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits.

Properties of synapses made by IVN command-interneurones in the stomatogastric ganglion of the spiny lobster Panulirus interruptus

1982 ◽  
Vol 97 (1) ◽  
pp. 153-168
Author(s):  
K. A. Sigvardt ◽  
B. Mulloney
Keyword(s):  
Membrane Potential ◽  
High Frequency ◽  
Spiny Lobster ◽  
Postsynaptic Membrane ◽  
Stomatogastric Ganglion ◽  
Gastric Mill ◽  
Panulirus Interruptus ◽  
Postsynaptic Potential ◽  
Lateral Posterior ◽  
Conductance Increase

1. The IVN command interneurones synapse directly onto 11 identified neurones in the stomatogastric ganglion: the two pyloric dilators (PDs), the anterior burster (AB), ventricular dilator (VD), the four gastric mill neurones (GMs), the two lateral posterior gastric neurones (LPGNs), and Interneurone I (Int 1). 2. The IVN p.s.p.s in PD and AB are biphasic, and consist of a fast depolarizing component followed by a slower hyperpolarizing component. 3. The hyperpolarizing component of this biphasic postsynaptic potential is inhibitory, and appears to be the result of a conductance increase to K+ and Cl-. 4. The IVN p.s.p. in VD is excitatory and can drive VD one-for-one. 5. The IVN p.s.p.s in GM and LPGN are inhibitory. The amplitude of a single p.s.p. is small but, at high frequency, summation of p.s.p.s holds the postsynaptic membrane potential below threshold. 6. The facilitation characteristics of the p.s.p.s in each neurone are described. 7. The functional significance of these synaptic characteristics is discussed in terms of the modification of motor output caused by a burst of the IVN interneurones.

Dopamine Modulates Graded and Spike-Evoked Synaptic Inhibition Independently at Single Synapses in Pyloric Network of Lobster

1998 ◽  
Vol 79 (4) ◽  
pp. 2063-2069 ◽  
Author(s):  
Amir Ayali ◽  
Bruce R. Johnson ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Action Potential ◽  
Spiny Lobster ◽  
Motor Pattern ◽  
Input Resistance ◽  
Stomatogastric Ganglion ◽  
Synaptic Inhibition ◽  
Panulirus Interruptus ◽  
Pyloric Network ◽  
Bath Application ◽  
Postsynaptic Cell

Ayali, Amir, Bruce R. Johnson, and Ronald M. Harris-Warrick. Dopamine modulates graded and spike-evoked synaptic inhibition independently at single synapses in pyloric network of lobster. J. Neurophysiol. 79: 2063–2069, 1998. Bath application of dopamine (DA) modifies the rhythmic motor pattern generated by the pyloric network in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Synaptic transmission between network members is an important target of DA action. All pyloric neurons employ both graded transmitter release and action-potential–mediated synaptic inhibition. DA was previously shown to alter the graded synaptic strength of every pyloric synapse. In this study, we compared DA's effects on action-potential–mediated and graded synaptic inhibition at output synapses of the lateral pyloric (LP) neuron. At each synapse the postsynaptic cell tested was isolated from other descending and pyloric synaptic inputs. DA caused a reduction in the size of the LP spike-evoked inhibitory postsynaptic potentials (IPSPs) in the pyloric dilator (PD) neuron. The change in IPSP size was significantly and linearly correlated with DA-induced reduction in the input resistance of the postsynaptic PD neuron. In contrast, graded inhibition, tested in the same preparations after superfusing the stomatogastric ganglion (STG) with tetrodotoxin (TTX), was consistently enhanced by DA. DA shifted the amplitude of spike-evoked IPSPs in the same direction as the alteration of the postsynaptic cell input resistance at two additional synapses tested: DA weakened the LP spike-mediated inhibition of the ventricular dilator (VD) and reduced the VD input resistance, while strengthening the LP → pyloric constrictor (PY) synapse and increasing PY input resistance. As previously reported, graded inhibition was enhanced at these two LP output synapses. We conclude that DA can differentially modulate the spike-evoked and graded components of synapses between members of a central pattern generator network. At the synapses we studied, actions on the presynaptic cell predominate in the modulation of graded transmission, whereas effects on postsynaptic cells predominate in the regulation of spike-evoked IPSPs.

Amine Modulation of the Transient Potassium Current in Identified Cells of the Lobster Stomatogastric Ganglion

2001 ◽  
Vol 86 (6) ◽  
pp. 2957-2965 ◽  
Author(s):  
Jack H. Peck ◽  
Stan T. Nakanishi ◽  
Ross Yaple ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Firing Rate ◽  
Voltage Clamp ◽  
Potassium Current ◽  
Stomatogastric Ganglion ◽  
Model System ◽  
Panulirus Interruptus ◽  
Pyloric Network ◽  
Electrode Voltage ◽  
Postinhibitory Rebound ◽  
Ionic Changes

The pyloric network of the stomatogastric ganglion of the lobster Panulirus interruptus is a model system used to understand how motor networks change their output to produce a variety of behaviors. The transient potassium current ( I A) shapes the activity of individual pyloric neurons by affecting their rate of postinhibitory rebound and spike frequency. We used two electrode voltage clamp to study the modulatory effects of dopamine (DA), octopamine (OCT), and serotonin (5-HT) on I A in the anterior burster (AB), inferior cardiac (IC), and ventricular dilator (VD) neurons of the pyloric circuit. DA significantly reduced I A in the AB and IC neurons and shifted their voltages of activation ( V act) and inactivation ( V inact) in a depolarized direction. These ionic changes contribute to the depolarization and increased firing rate of the AB and IC neurons produced by DA. Likewise, 5-HT significantly reduced I A and shifted V inact in the depolarized direction in the IC neuron, consistent with 5-HT's enhancement of IC firing. None of the amines evoked significant changes in I A in the VD neuron, suggesting that other currents mediate the amine effects on this neuron.

Aminergic modulation in lobster stomatogastric ganglion. II. Target neurons of dopamine, octopamine, and serotonin within the pyloric circuit

1986 ◽  
Vol 55 (5) ◽  
pp. 866-881 ◽  
Author(s):  
R. E. Flamm ◽  
R. M. Harris-Warrick
Keyword(s):  
Neural Circuit ◽  
Lucifer Yellow ◽  
Spiny Lobster ◽  
Motor Pattern ◽  
Preceding Paper ◽  
Cell Types ◽  
Stomatogastric Ganglion ◽  
Synaptic Organization ◽  
Potential Oscillations ◽  
Panulirus Interruptus

In the preceding paper, we describe how dopamine, octopamine, and serotonin modulate the neural circuit generating a well-described motor pattern, the pyloric rhythm of the stomatogastric ganglion in the spiny lobster, Panulirus interruptus. In this paper, we identify the neurons within the pyloric circuit that are directly affected by each amine. We accomplished this by isolating each pyloric neuron from all known synaptic input, using a combination of Lucifer yellow photoinactivation of presynaptic neurons and pharmacological blockade by pyloric neurotransmitters. Dopamine, octopamine, and serotonin were bath applied to the preparation, and the responses of synaptically isolated neurons were recorded. Each amine had a unique constellation of effects on the neurons of the pyloric circuit. Almost every neuron in the circuit was directly affected by each amine. Dopamine and octopamine modulated every neuron, whereas serotonin affected four of the six cell types. Each amine had multiple effects among pyloric neurons including the induction of endogenous rhythmic bursting activity, initiation or enhancement of tonic firing activity, and inhibition accompanied by hyperpolarization. All three amines induced rhythmic bursting in one neuron (the AB neuron), but the form of the underlying slow-wave membrane-potential oscillations was different with octopamine than with dopamine and serotonin. Our knowledge of the effects of each amine on each pyloric neuron, combined with the extensive knowledge of the synaptic organization of the pyloric circuit, has allowed us to explain qualitatively the major aspects of the unique variants of the pyloric motor rhythm that each amine produces in the synaptically intact circuit.

scholarly journals Dopamine Modulation of Two Delayed Rectifier Potassium Currents in a Small Neural Network

2005 ◽  
Vol 94 (4) ◽  
pp. 2888-2900 ◽  
Author(s):  
Matthias Gruhn ◽  
John Guckenheimer ◽  
Bruce Land ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Motor Neurons ◽  
Spiny Lobster ◽  
Potassium Currents ◽  
Cell Types ◽  
Spike Frequency ◽  
Differential Sensitivity ◽  
Single Type ◽  
Delayed Rectifier ◽  
Panulirus Interruptus ◽  
Pyloric Dilator

Delayed rectifier potassium currents [ IK(V)] generate sustained, noninactivating outward currents with characteristic fast rates of activation and deactivation and play important roles in shaping spike frequency. The pyloric motor network in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, is made up of one interneuron and 13 motor neurons of five different classes. Dopamine (DA) increases the firing frequencies of the anterior burster (AB), pyloric (PY), lateral pyloric (LP), and inferior cardiac (IC) neurons and decreases the firing frequencies of the pyloric dilator (PD) and ventricular dilator (VD) neurons. In all six types of pyloric neurons, IK(V) is small with respect to other K+ currents. It is made up of at least two TEA-sensitive components that show differential sensitivity to 4-aminopyridine and quinidine, and have differing thresholds of activation. One saturable component is activated at potentials above −25 mV, whereas the second component appears at more depolarized voltages and does not saturate at voltage steps up to +45 mV. The magnitude of the components varies among cell types but also shows considerable variation within a single type. A subset of PY neurons shows a marked enhancement in spike frequency with DA; DA evokes a pronounced reversible increase in IK(V) conductance of ≤30% in the PY neurons studied, and on average significantly increases both components of IK(V). The AB neuron also shows a reversible 20% increase in the steady state IK(V). DA had no effect on IK(V) in PD, LP, VD, and IC neurons. The physiological roles of these currents and their modulation by DA are discussed.

Pharmacological dissection of pyloric network of the lobster stomatogastric ganglion using picrotoxin

1980 ◽  
Vol 44 (6) ◽  
pp. 1089-1101 ◽  
Author(s):  
M. Bidaut
Keyword(s):  
Stomatogastric Ganglion ◽  
Inhibitory Synapses ◽  
Primary Role ◽  
Panulirus Interruptus ◽  
Pyloric Network ◽  
Pyloric Dilator ◽  
Fast Rise ◽  
Later Phase ◽  
Pyloric Rhythm

1. Picrotoxin (PTX) (10(-7)-10(-6) M) completely blocked most inhibitory synapses in the pyloric pattern generator of the lobster (Panulirus interruptus) stomatogastric ganglion. The sensitivity of synapses from most classes of identified neurons was examined. Blockade was at least partly reversible with prolonged washing. 2. The synapses from pyloric dilator (PD) neurons were the only inhibitory synapses that picrotoxin failed to block completely. 3. A correlation is derived that brief, fast-rise inhibitory postsynaptic potentials (IPSPs) are picrotoxin sensitive, whereas a slow rounded component of IPSPs from PD neurons is not picrotoxin sensitive. 4. Picrotoxin caused specific changes in the pattern of the motor rhythm produced by the 16-cell pyloric network. This sheds some light on the functional role of particular synapses in the pyloric generator. 5. The endogenously bursting neurons (PD and anterior burster (AB)), which drive the pyloric rhythm, kept a similar burst rate. 6. Under picrotoxin, the pyloric "follower" neurons all moved to later phase relative to the "driver" group. Some normally antagonistic cells, related by reciprocal inhibitor connections, became in-phase. These and other pattern changes could be related to blockade of particular synapses. 7. The pyloric rhythm was still quite recognizable under picrotoxin despite the drastically altered circuitry of the synaptic network. This supports the idea that periodic inhibition from the PD driver neurons plays a primary role in creating the pyloric pattern.

scholarly journals Variation in sodium current amplitude between vasopressin and oxytocin hypothalamic supraoptic neurons

2013 ◽  
Vol 109 (4) ◽  
pp. 1017-1024 ◽  
Author(s):  
Reese Scroggs ◽  
Lie Wang ◽  
Ryoichi Teruyama ◽  
William E. Armstrong
Keyword(s):  
Time Course ◽  
Sodium Current ◽  
Recovery From Inactivation ◽  
Double Exponential ◽  
Significant Difference ◽  
Steady State Inactivation ◽  
Neuronal Types ◽  
Rate Of Recovery ◽  
Firing Properties ◽  
Supraoptic Neurons

Biophysical characteristics of tetrodotoxin-sensitive sodium (Na+) currents were studied in vasopressin (VP) and oxytocin (OT) supraoptic neurons acutely isolated from rat hypothalamus. Na+ current density (pA/pF) was significantly greater in VP neurons than in OT neurons. No significant difference between VP and OT neurons was detected regarding the voltage dependence of activation and steady-state inactivation, or rate of recovery from inactivation of Na+ currents. In both VP and OT neurons, the macroscopic inactivation of the Na+ currents was best fitted with a double-exponential expression suggesting two rates of inactivation. Also in both types, the time course of recovery from inactivation proceeded with fast and slow time constants averaging around 8 and 350 ms, respectively, suggesting the presence of multiple pathways of recovery from inactivation. The slower time constant of recovery of inactivation may be involved in the decrease in action potential (AP) amplitude that occurs after the first spike during burst firing in both neuronal types. The larger amplitude of Na+ currents in VP vs. OT neurons may explain the previous observations that VP neurons exhibit a lower AP threshold and greater AP amplitude than OT neurons, and may serve to differently tune the firing properties and responses to neuromodulators of the respective neuronal types.

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