scholarly journals The Effects of Polarizing Current on Nerve Terminal Impulses Recorded from Polymodal and Cold Receptors in the Guinea-pig Cornea

2002 ◽  
Vol 120 (3) ◽  
pp. 395-405 ◽  
Author(s):  
Richard W. Carr ◽  
Svetlana Pianova ◽  
James A. Brock
Keyword(s):  
Guinea Pig ◽  
Nerve Terminal ◽  
Sensory Nerve ◽  
Outward Current ◽  
Nerve Terminals ◽  
Functional Difference ◽  
Inward Current ◽  
Cold Receptor ◽  
Cold Receptors

It was reported recently that action potentials actively invade the sensory nerve terminals of corneal polymodal receptors, whereas corneal cold receptor nerve terminals are passively invaded (Brock, J.A., S. Pianova, and C. Belmonte. 2001. J. Physiol. 533:493–501). The present study investigated whether this functional difference between these two types of receptor was due to an absence of voltage-activated Na+ conductances in cold receptor nerve terminals. To address this question, the study examined the effects of polarizing current on the configuration of nerve terminal impulses recorded extracellularly from single polymodal and cold receptors in guinea-pig cornea isolated in vitro. Polarizing currents were applied through the recording electrode. In both receptor types, hyperpolarizing current (+ve) increased the negative amplitude of nerve terminal impulses. In contrast, depolarizing current (−ve) was without effect on polymodal receptor nerve terminal impulses but increased the positive amplitude of cold receptor nerve terminal impulses. The hyperpolarization-induced increase in the negative amplitude of nerve terminal impulses represents a net increase in inward current. In both types of receptor, this increase in inward current was reduced by local application of low Na+ solution and blocked by lidocaine (10 mM). In addition, tetrodotoxin (1 μM) slowed but did not reduce the hyperpolarization-induced increase in the negative amplitude of polymodal and cold nerve terminal impulses. The depolarization-induced increase in the positive amplitude of cold receptor nerve terminal impulses represents a net increase in outward current. This change was reduced both by lidocaine (10 mM) and the combined application of tetraethylammomium (20 mM) and 4-aminopyridine (1 mM). The interpretation is that both polymodal and cold receptor nerve terminals possess high densities of tetrodotoxin-resistant Na+ channels. This finding suggests that in cold receptors, under normal conditions, the Na+ conductances are rendered inactive because the nerve terminal region is relatively depolarized.

Cl− Accumulation Does Not Account for the Depolarizing Phase of the Synaptic GABA Response in Hippocampal Pyramidal Cells

1999 ◽  
Vol 82 (2) ◽  
pp. 768-777 ◽  
Author(s):  
Katherine L. Perkins
Keyword(s):  
Guinea Pig ◽  
Short Interval ◽  
Outward Current ◽  
Pyramidal Cells ◽  
Equilibrium Potential ◽  
Inward Current ◽  
Postsynaptic Currents ◽  
Current Curve ◽  
Separate Channel ◽  
Channel Type

It has been proposed that the depolarizing phase of the biphasic synaptic GABA response could be mediated by HCO3 − passing through GABAA channels after dissipation of the transmembrane Cl− gradient due to intracellular Cl− accumulation. To test this hypothesis, giant GABA-mediated postsynaptic currents (GPSCs) were recorded from pyramidal cells in slices of adult guinea pig hippocampus in the presence of 4-aminopyridine. GPSCs consisted of an early outward current (GABAA component) followed by a late inward current (GABAD component). Spontaneous outward inhibitory postsynaptic currents (IPSCs) occurred during the GABADcomponent of the GPSC. GPSCs that were evoked 1–12 s after the preceding GPSC (short interval, siGPSCs) showed no GABADcomponent even though in many cells the amplitude of the siGPSC was greater than the amplitude of the GABAA component of the preceding spontaneous GPSC. In addition, the siGPSC evoked during the GABAD component of a spontaneous GPSC was an outward current. To test whether the siGPSC lacked a GABADcomponent because it was generated predominantly at the soma, where less of an increase in [Cl−]i would occur, picrotoxin was applied to the soma of the pyramidal cell. To the contrary, this focal application of picrotoxin caused less of a reduction in the amplitude of the siGPSC than in the amplitude of the GABAA component of the GPSC. Furthermore when a GPSC and siGPSC were evoked 10 s apart using identical stimuli, the area under the outward current curve was sometimes greater for the siGPSC than for the GPSC, and yet the siGPSC had no inward component. This result indicates that even when the location of Cl− entry was the same, more Cl− could enter the cell during the siGPSC than during the outward component of the GPSC and yet not lead to an inward current. In addition, when the second of two identical stimuli was applied during the inward GABAD component of the first evoked GPSC, the GABAA response it generated was always outward, demonstrating that the equilibrium potential for GABAA responses did not become more positive than the holding potential during a GPSC. Finally, evoking GPSCs at a hyperpolarized potential revealed that the siGPSC actually lacked a GABAD conductance. These results disprove the Cl− accumulation hypothesis of the synaptic depolarizing GABA response and suggest the possibility that a separate channel type may mediate the GABAD component of the GPSC.

Guinea pig visceral C-fiber neurons are diverse with respect to the K+ currents involved in action-potential repolarization

1994 ◽  
Vol 71 (2) ◽  
pp. 561-574 ◽  
Author(s):  
E. P. Christian ◽  
J. Togo ◽  
K. E. Naper
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Outward Current ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Whole Cell ◽  
C Fiber ◽  
K Current ◽  
Action Potential Repolarization

1. Intracellular recordings were made from C-fiber neurons identified by antidromic conduction velocity in intact guinea pig nodose ganglia maintained in vitro, and whole-cell patch clamp recordings were made from dissociated guinea pig nodose neurons to investigate the contribution of various K+ conductances to action-potential repolarization. 2. The repolarizing phase of the intracellularly recorded action potential was prolonged in a concentration-dependent manner by charybdotoxin (Chtx; EC50 = 39 nM) or iberiatoxin (Ibtx; EC50 = 48 nM) in a subpopulation of 16/36 C-fiber neurons. In a subset of these experiments, removal of extracellular Ca2+ reversibly prolonged action-potential duration (APD) in the same 4/9 intracellularly recorded C-fiber neurons affected by Chtx (> or = 100 nM). These convergent results support that a Ca(2+)-activated K+ current (IC) contributes to action-potential repolarization in a restricted subpopulation of C-fiber neurons. 3. Tetraethylammonium (TEA; 1-10 mM) increased APD considerably further in the presence of 100-250 nM Chtx or Ibtx, or in nominally Ca(2+)-free superfusate in 14/14 intracellularly recorded C-fiber neurons. TEA affected APD similarly in subpopulations of neurons with and without IC, suggesting that a voltage-dependent K+ current (IK) contributes significantly to action-potential repolarization in most nodose C-fiber neurons. 4. Substitution of Mn2+ for Ca2+ reduced outward whole-cell currents elicited by voltage command steps positive to -30 mV (2-25 ms) in a subpopulation of 21/36 dissociated nodose neurons, supporting the heterogeneous expression of IC. The kinetics of outward tail current relaxations (tau s of 1.5-2 ms) measured at the return of 2-3 ms depolarizing steps to -40 mV were indistinguishable in neurons with and without IC, precluding a separation of the nodose IC and IK by a difference in deactivation rates. 5. Chtx (10-250 nM) reduced in a subpopulation of 3/8 C-fiber neurons the total outward current elicited by voltage steps depolarized to -30 mV in single microelectrode voltage-clamp recordings. TEA (5-10 mM) further reduced outward current in the presence of 100-250 nM Chtx in all eight experiments. The Chtx-sensitive current was taken to represent IC, and the TEA-sensitive current, the IK component contributing to action-potential repolarization. 6. Rapidly inactivating current (IA) was implicated in action-potential repolarization in a subpopulation of intracellularly recorded C-fiber neurons. In 4/7 neurons, incremented hyperpolarizing prepulses negative to -50 mV progressively shortened APD.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulation of neuropeptide release

1980 ◽  
Vol 210 (1178) ◽  
pp. 91-111 ◽  
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Gaba Receptors ◽  
Opiate Receptors ◽  
Sensory Nerve ◽  
Substantia Gelatinosa ◽  
Nerve Terminals ◽  
Analgesic Effects ◽  
Spinal Cord Level

The demonstration of depolarization-induced release of substance P, Met- and Leu-enkephalin, somatostatin, neurotensin, vasoactive intestinal polypeptide and cholecystokinin-like material from various regions of rat brain in vitro supports the hypothesis that these and other neuropeptides may act as neurotransmitters. In each case the stimulusevoked release, but not the basal release, of peptide was dependent on the presence of calcium ions in the external medium. The stimulus-evoked release of substance P from nerve terminals in rat substantia nigra may be regulated by presynaptic γ -aminobutyric acid (GABA) receptors. The possible existence of presynaptic opiate receptors on substance P-containing sensory nerve terminals may offer an explanation for the analgesic effects of opiates at spinal cord level, and for the existence of enkephalin neurons in substantia gelatinosa. Capsaicin releases substance P from spinal cord nerve terminals and may impair their function, while having no effect on substance P neurons in supraspinal regions. The possibility of cosecretion of peptide and amine products from the same cells is discussed.

Loss of mGluR-mediated hyperpolarizations and increase in mGluR depolarizations in basolateral amygdala neurons in kindling-induced epilepsy

1996 ◽  
Vol 76 (4) ◽  
pp. 2808-2812 ◽  
Author(s):  
K. H. Holmes ◽  
N. B. Keele ◽  
P. Shinnick-Gallagher
Keyword(s):  
Basolateral Amygdala ◽  
Metabotropic Glutamate Receptor ◽  
Maximum Amplitude ◽  
Outward Current ◽  
Response Relationship ◽  
Inward Current ◽  
Group I ◽  
Hyperpolarizing Response ◽  
Group Ii

1. Intracellular recordings were made from neurons of the basolateral amygdala (BLA) in in vitro slice preparations to determine long-term differences in metabotropic glutamate receptor (mGluR) agonist-induced membrane responses in control and amygdala-kindled rats. 2. (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine-1 (L-CCG-I; 100 microM) typically evoked a hyperpolarization/outward current in control BLA neurons; the hyperpolarization is mediated through a group-II-like mGluR subtype of receptor and is recorded in accommodating neurons that cease firing in the presence of a long (400 ms) depolarizing current injection (0.5 nA). In amygdala-kindled slices, L-CCG-I (100 microM) hyperpolarized only 1 of 13 BLA neurons. 3. 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (100 microM) elicited a hyperpolarization/depolarization (outward/inward current) in control neurons and evoked only a membrane depolarization (inward current) in kindled BLA neurons; this depolarization is similar to that mediated by group I mGluR activation in other neurons. 4. In control nonaccommodating neurons the concentration-response relationship for the 1S,3R-ACPD-induced inward current had a median effective concentration (EC50) of 49 microM and a maximum amplitude of 182 +/- 30 (mean +/- SE) pA. In kindled nonaccommodating neurons the EC50 of the concentration-response relationship for 1S,3R-ACPD was shifted to 29 microM and the maximum value increased to 265 +/- 15 pA, reflecting an increase in efficacy. 5. These data suggest that amygdala kindling causes lasting changes in mGluR responses in the BLA reflecting a downregulation of a group-II-like mGluR subtype mediating the hyperpolarizing response and an upregulation of a group I mGluR1 or 5 subtype. The hyperpolarizing response reduced by kindling and the increase in the group I mGluR response may reflect an alteration in the balance between inhibition and excitation and may contribute to the transition to epileptiform bursting in kindled neurons.

Capsaicin-sensitive afferent nerves activate submucosal secretomotor neurons in guinea pig ileum

1995 ◽  
Vol 269 (2) ◽  
pp. G203-G209 ◽  
Author(s):  
S. Vanner ◽  
W. K. MacNaughton
Keyword(s):  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Guinea Pig Ileum ◽  
Secretomotor Neurons

This study examined whether capsaicin-sensitive sensory nerves regulate intestinal ion transport using both Ussing chamber and intracellular recording techniques in in vitro submucosal preparations from the guinea pig ileum. In Ussing chamber studies, serosal application of capsaicin (20 nM-20 microM) evoked a biphasic dose-dependent increase in short-circuit current (Isc) (maximal effective concentration 200 nM and 2 microM, respectively). In chloride-free buffer, capsaicin responses were significantly reduced. Capsaicin evoked little or no response when extrinsic sensory nerve fibers had been surgically removed and tetrodotoxin and low-calcium and high-magnesium solutions blocked responses to capsaicin. In epithelial preparations devoid of submucosal neurons, capsaicin had virtually no effect, suggesting that responses evoked by capsaicin-sensitive nerves result from activation of submucosal secretomotor neurons. Intracellular recordings from single submucosal neurons demonstrated that superfusion with capsaicin (2 microM) depolarized neurons with an associated decreased conductance. Depolarizations were completely desensitized when capsaicin was reapplied, but synaptic inputs were unaffected. This study suggests that capsaicin-sensitive nerves can regulate ion transport in the gastrointestinal tract by release of neurotransmitter(s) that activate submucosal secretomotor neurons.

Ischemia But Not Anoxia Evokes Vesicular and Ca2+-Independent Glutamate Release In the Dorsal Vagal Complex In Vitro

2000 ◽  
Vol 83 (5) ◽  
pp. 2905-2915 ◽  
Author(s):  
Anna Kulik ◽  
Stefan Trapp ◽  
Klaus Ballanyi
Keyword(s):  
Glutamate Uptake ◽  
Glutamate Release ◽  
Outward Current ◽  
Cyclopiazonic Acid ◽  
Synaptic Activity ◽  
Dorsal Vagal Complex ◽  
Free Solution ◽  
Inward Current ◽  
Metabolic Arrest

Whole cell recordings of fura-2 dialyzed vagal neurons of brain stem slices were used to monitor interstitial glutamate accumulation within the dorsal vagal complex. Anoxia produced a sustained outward current (60 pA) and a moderate [Ca2+]i rise (40 nM). These responses were neither mimicked by [1S,3R]-1-aminocyclo-pentane-1,3-dicarboxylic acid nor affected by Ca2+-free solution, 6-cyano-7-nitroquino-xaline-2,3-dione (CNQX), 2-amino-5-phosphonovalerate (APV), or tetrodotoxin. Anoxia or cyanide in glucose-free saline (in vitro ischemia) as well as ouabain or iodoacetate elicited an initial anoxia-like [Ca2+]i increase that turned after several minutes into a prominent Ca2+ transient (0.9 μM) and inward current (−1.8 nA). APV plus CNQX (plus methoxyverapamil) inhibited this inward current as well as accompanying spontaneous synaptic activity, and reduced the secondary [Ca2+]i rise to values similar to those during anoxia. Each of the latter drugs delayed onset of both ischemic current and prominent [Ca2+]i rise by several minutes and attenuated their magnitudes by up to 40%. Ca2+-free solution induced a twofold delay of the ischemic inward current and suppressed the prominent Ca2+ increase but not the initial moderate [Ca2+]i rise. Cyclopiazonic acid or arachidonic acid in Ca2+-free saline delayed further the ischemic current, whereas neither inhibitors of glutamate uptake (dihydrokainate,d,l-threo-β-hydroxyaspartate,l-transpyrrolidone-2,4-dicarboxylate) nor the Cl− channel blocker 5-nitro-2-(3-phenylpropyl-amino) benzoic acid had any effect. In summary, the response to metabolic arrest is due to activation of ionotropic glutamate receptors causing Ca2+ entry via N-methyl-d-aspartate receptors and voltage-activated Ca2+ channels. An early Ca2+-dependent exocytotic phase of ischemic glutamate release is followed by nonvesicular release, not mediated by reversed glutamate uptake or Cl− channels. The results also show that glycolysis prevents glutamate release during anoxia.

Mechanism of block by ZD 7288 of the hyperpolarization-activated inward rectifying current in guinea pig substantia nigra neurons in vitro

1995 ◽  
Vol 74 (6) ◽  
pp. 2366-2378 ◽  
Author(s):  
N. C. Harris ◽  
A. Constanti
Keyword(s):  
Substantia Nigra ◽  
Guinea Pig ◽  
Voltage Clamp ◽  
Time Constant ◽  
Slow Inward Current ◽  
Current Clamp ◽  
Inward Current ◽  
Electrotonic Potential ◽  
Zd 7288

1. The effects of the novel bradycardic agent 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD 7288) (Zeneca) were investigated on the hyperpolarization-activated cationic current (Ih) in guinea pig substantia nigra pars compacta neurons in vitro, using a single-microelectrode current-clamp/voltage-clamp technique. 2. Under current-clamp conditions, injection of large negative current pulses (0.1-0.5 nA, 400 ms) evoked a slow depolarizing "sag" in the electrotonic potential due to activation of the slow inward (anomalous) rectifier. In voltage-clamp recordings, hyperpolarizing voltage steps from a holding potential of -60 mV (close to resting potential) elicited slow inward current relaxations with kinetic properties similar to those seen for other neuronal Ihs. 3. ZD 7288 (10-100 microM) produced a consistent abolition of the electrotonic potential sag with no effect on membrane potential or spike properties. Under voltage clamp, Ih amplitude was clearly reduced in a time- and concentration-dependent manner (apparent half-maximum blocking concentration = 2 microM); full block of Ih was typically achieved after 10-15 min of exposure to 50 microM ZD 7288, with no significant recovery observed after 1 h of washing. 4. A similar (although more rapid) block of Ih was seen after application of 3-5 mM Cs+ (partially reversible after 30 min of washing). 5. Partial block of Ih by 10 microM ZD 7288 was accompanied by a reduction in the maximum amplitude of the Ih activation curve, a small negative shift in its position on the voltage axis, and a linearization of the steady-state current-voltage relationship. The estimated Ih reversal potential, however, remained unaffected. 6. In 10 microM ZD 7288, the time course of Ih activation and deactivation was significantly slowed (within the range of -70 to -120 mV for the activation time constant and -70 to -90 mV for the inactivation time constant). 7. Blockade of Ih by ZD 7288 or Cs+ was independent of prior Ih activation (i.e., non-use dependent). 8. Intracellular loading with ZD 7288 also abolished the sag in the electrotonic voltage response and Ih relaxations, suggesting an intracellular site of action. By contrast, intracellular Cs+ had no effect on Ih properties. 9. Block of Ih by ZD 7288 (but not Cs+) was relieved by prolonged cell hyperpolarization, manifested as a slowly developing (half-time approximately 20 s) inward current at a holding potential of -100 mV. 10. We propose that ZD 7288, when applied externally, may behave as a "lipophilic" quaternary cation, capable of passing into the cell interior to block Ih channels in their closed state; this compound may thus prove a useful research tool, in place of Cs+, for studying the properties and significance of Ih currents in controlling neuronal function.

TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus

2009 ◽  
Vol 296 (2) ◽  
pp. G255-G265 ◽  
Author(s):  
Shaoyong Yu ◽  
Ann Ouyang
Keyword(s):  
Guinea Pig ◽  
Action Potentials ◽  
Transient Receptor Potential ◽  
Ex Vivo ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Peripheral Sensitization ◽  
Nerve Terminals ◽  
Mechanical Hypersensitivity ◽  
C Fibers

Bradykinin (BK) activates sensory nerves and causes hyperalgesia. Transient receptor potential A1 (TRPA1) is expressed in sensory nerves and mediates cold, mechanical, and chemical nociception. TRPA1 can be activated by BK. TRPA1 knockout mice show impaired responses to BK and mechanical nociception. However, direct evidence from sensory nerve terminals is lacking. This study aims to determine the role of TRPA1 in BK-induced visceral mechanical hypersensitivity. Extracellular recordings of action potentials from vagal nodose and jugular neurons are performed in an ex vivo guinea pig esophageal-vagal preparation. Peak frequencies of action potentials of afferent nerves evoked by esophageal distension and chemical perfusion are recorded and compared. BK activates most nodose and all jugular C fibers. This activation is repeatable and associated with a significant increase in response to esophageal distension, which can be prevented by the B2 receptor antagonist WIN64338. TRPA1 agonist allyl isothiocyanate (AITC) activates most BK-positive nodose and jugular C fibers. This is associated with a transient loss of response to mechanical distensions and desensitization to a second AITC perfusion. Desensitization with AITC and pretreatment with TRPA1 inhibitor HC-030031 both inhibit BK-induced mechanical hypersensitivity but do not affect BK-evoked activation in nodose and jugular C fibers. In contrast, esophageal vagal afferent Aδ fibers do not respond to BK or AITC and fail to show mechanical hypersensitivity after BK perfusion. This provides the first evidence directly from visceral sensory afferent nerve terminals that TRPA1 mediates BK-induced mechanical hypersensitivity. This reveals a novel mechanism of visceral peripheral sensitization.

Two electrophysiologically distinct types of cultured pacemaker cells from rabbit sinoatrial node

1986 ◽  
Vol 250 (2) ◽  
pp. H325-H329 ◽  
Author(s):  
R. D. Nathan
Keyword(s):  
Sinoatrial Node ◽  
Sodium Current ◽  
Outward Current ◽  
Slow Inward Current ◽  
Transient Outward Current ◽  
Type I ◽  
Pacemaker Cells ◽  
Inward Current ◽  
Fast Transient

Previous investigations employing multicellular nodal preparations (i.e., mixtures of dominant and subsidiary pacemaker cells) have suggested that the fast transient inward sodium current (iNa) either is not present in dominant pacemaker cells or is present but inactivated at the depolarized take-off potentials that these cells exhibit. In the present study, this question was resolved by voltage clamp analysis of single pacemaker cells isolated from the sinoatrial node and maintained in vitro for 1-3 days. Two types of cells, each with a different morphology, exhibited two modes of electrophysiological behavior. Type I cells (presumably dominant pacemakers) displayed only a tetrodotoxin (TTX)-resistant (but cadmium-sensitive) slow inward current, whereas type II cells (presumably subsidiary pacemakers) exhibited two components of inward current, a TTX-sensitive, fast transient inward current and a TTX-resistant (but cadmium-sensitive) slow inward current. Three other voltage-gated currents, 1) a slowly developing inward current activated by hyperpolarization (if, ih, delta ip), 2) a transient outward current activated by strong depolarization (ito, iA), and 3) a delayed outward current, were recorded in both types of pacemaker cells.

Electrical activity of mouse motor nerve terminals

1984 ◽  
Vol 222 (1226) ◽  
pp. 115-120 ◽  
Keyword(s):  
Electrical Activity ◽  
Transmitter Release ◽  
Motor Nerve ◽  
Extracellular Recording ◽  
Nerve Terminals ◽  
Motor Nerve Terminals ◽  
Inward Current ◽  
Recent Claim

Focal extracellular recording was made from presynaptic motor nerve terminals made visible directly in in vitro preparations of mouse intercostalis intimi muscles. The demonstration of a net inward current distally in these terminals at sites of transmitter release allow the conclusion that the mammalian terminal is electrically excitable, contrary to a recent claim that it is not.

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