Dihydropyridine actions on calcium currents of frog sympathetic neurons

Jones, Stephen; Jacobs, L.

doi:10.1523/jneurosci.10-07-02261.1990

Cited by 102 publications

(77 citation statements)

References 30 publications

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“…In the present study, nimodipine blocked ϳ17% of I Ca , suggesting the presence of L-type Ca channels as well. Although we did not test the effect of nimodipine on release, application of nimodipine and -CgTX had no greater blocking effect than -CgTX alone, suggesting that both agents may work on the same channels, for which there is some precedent (Jones and Jacobs, 1990;Wang et al, 1992;Reeve et al, 1994). The remaining -CgTX-insensitive current has not been identified but was not blocked by -AGA-IVA; therefore, it was apparently not P-type (Mintz et al, 1992).…”

Section: Types Of Ca Channels and Their Coupling To Transmitter Releasementioning

confidence: 80%

Direct Measurements of Presynaptic Calcium and Calcium-Activated Potassium Currents Regulating Neurotransmitter Release at CulturedXenopusNerve–Muscle Synapses

et al. 1997

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The understanding of neurotransmitter release at vertebrate synapses has been hampered by the paucity of preparations in which presynaptic ionic currents and postsynaptic responses can be monitored directly. We used cultured embryonic Xenopus neuromuscular junctions and simultaneous pre-and postsynaptic patch-clamp current-recording procedures to identify the major presynaptic conductances underlying the initiation of neurotransmitter release.Step depolarizations and action potential waveforms elicited Na and K currents along with Ca and Ca-activated K (K Ca ) currents. The onset of K Ca current preceded the peak of the action potential. The predominantly -CgTX GVIA-sensitive Ca current occurred primarily during the falling phase, but there was also significant Ca 2ϩ entry during the rising phase of the action potential. The postsynaptic current began a mean of 0.7 msec after the time of maximum rate of rise of the Ca current. -CgTX also blocked K Ca currents and transmitter release during an action potential, suggesting that Ca and K Ca channels are colocalized at presynaptic active zones. In double-ramp voltage-clamp experiments, K Ca channel activation is enhanced during the second ramp. The 1 msec time constant of decay of enhancement with increasing interpulse interval may reflect the time course of either the deactivation of K Ca channels or the diffusion/removal of Ca 2ϩ from sites of neurotransmitter release after an action potential. Key word: neuromuscular junction; nerve terminal; calcium channel; charybdotoxin; conotoxin; synaptic delayNeurotransmitter release from nerve terminals is triggered by the entry of Ca 2ϩ through voltage-gated Ca channels (Katz, 1969;Augustine et al., 1987). Our understanding of the relationship between the presynaptic ionic currents and release is based largely on studies of the squid giant synapse (Katz and Miledi, 1967;Llinás et al., 1981;Charlton et al., 1982; Augustine et al., 1985a,b). Several critical questions remain, however, that one would like to address with equivalent biophysical rigor at a vertebrate synapse in which the presynaptic ionic currents and postsynaptic currents can be measured simultaneously and release can be resolved at the single quantum level. In this report we take advantage of a neuromuscular synapse preparation in which this can be done.Among the important pending questions are the timing and delay between Ca 2ϩ entry during an action potential and release, the roles of different Ca and Ca-activated K (K Ca ) channels in the release process, and the quantitative relationship between Ca 2ϩ influx and release. In squid, it has been shown that Ca 2ϩ enters principally during the repolarization phase of the action potential (Llinás et al., 1982). Physiological studies of various excitable secretory cells have shown that different types of Ca channels play a dominant role in triggering release in different terminals, and often multiple Ca channel types are present in any given terminal (Kerr and Yoshikami, 1984;Pfrieger et al., 1992, Luebke et al...

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Section: Types Of Ca Channels and Their Coupling To Transmitter Releasementioning

confidence: 80%

Direct Measurements of Presynaptic Calcium and Calcium-Activated Potassium Currents Regulating Neurotransmitter Release at CulturedXenopusNerve–Muscle Synapses

et al. 1997

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“…The WCgTX-sensitive component showed a significantly enhanced contribution to the total current in NGF-differentiated PC12 cells (P = 0-001) and in v-src 37 'C differentiated PC12 cells (P = 0-01) when compared to their controls. pyridine-sensitive L-type Ca2" channels (Hirning et al 1988;Plummer et al 1989;Jones & Jacobs, 1990;Ikeda, 1991). We have found that 68 % of the whole-cell Ca2+ current in PC12 cells differentiated with NGF was ao-CgTX sensitive and that 52 % of the whole-cell Ca21 current in PC12 cells expressing a temperature-sensitive v-src protein was wo-CgTX sensitive.…”

Section: Morphologymentioning

confidence: 94%

Enhanced expression of Ca2+ channels by nerve growth factor and the v‐src oncogene in rat phaeochromocytoma cells.

Lewis

Aizpurua

Rausch

1993

The Journal of Physiology

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SUMMARY1. Rat phaeochromocytoma (PC12) cells were used to investigate the expression of Ca2" channel types during neuronal differentiation. Neuronal differentiation was induced by treatment with nerve growth factor (NGF) or by activation of a temperature-sensitive tyrosine kinase (pp60v"8Tc) in genetically modified PC12 (PC12/v-src) cells. PC12 cells differentiated morphologically in the presence of NGF. When grown at the permissive temperature of 37 TC which activates the kinase activity of pp60v-rc, PC12/v-src cells differentiated morphologically with the extension of neurites. In contrast, PC12/v-src cells grown at the non-permissive temperature of 40 'C continued to divide and were morphologically indistinguishable from control PC12 cells.2. Whole-cell Ca2+ currents were measured in PC12 cells using Ba2+ as the charge carrier. Ba2+ currents measured at the peak of the current-voltage curve from a holding potential of -80 mV were -0-28 + 004 nA (mean +s.E.M.) in control PC12 cells compared to -1-25+0-16 nA in NGF-differentiated cells. The current density increased from 9-4 + 0 7 pA/pF in control PC12 cells to 22-8 + 2-4 pA/pF in NGFdifferentiated PC12 cells. Ba2+ currents were -0-24 + 0-04 nA in undifferentiated PC12/v-src cells grown at the non-permissive temperature of 40 0C compared to -0-95 +016 nA in differentiated PC12/v-src cells grown at the permissive temperature of 37 'C. The current density increased from 4-5 + 0-5 pA/pF in PC12/vsrc cells grown at the non-permissive temperature of 40 'C to 13-3 + 24 pA/pF in PC12/v-src cells grown at the permissive temperature of 37 'C.3. The sensitivity of Ba2+ currents to w)-conotoxin GVIA (w)-CgTX) was determined for currents measured at the peak of the current-voltage curve (0 mV in 10 mm Ba2+) from a holding potential of -80 mV. In NGF-differentiated PC12 cells, 10 jtM CWCgTx inhibited 68-1+ 3-2 % of the total Ba2+ current compared to 35-9 +4-1% in control cells. The density of the w)-CgTX-sensitive current increased from 3-3 ± 04 pA/pF in control cells to 15-7 + 2-0 pA/pF in NGF-differentiated cells. In

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“…In addition, one must be careful when using P o as a criterion because both N-and L-channels are open much of the time at depolarized potentials (greater than or equal to ϩ30 mV). L-channels were found in 10 of 43 patches, which is surprisingly frequent because only ϳ5% of the whole-cell current is sensitive to DHP antagonists (Jones and Jacobs, 1990;Elmslie et al, 1992). However, L-channel density appeared to be lower than either Nor E f -channels because there was a larger fraction of single L-channel patches (7/17).…”

Section: L-channelsmentioning

confidence: 97%

“…In frog sympathetic neurons, the calcium current recorded in 2 mM Ba 2ϩ is primarily N-type because ϳ90% of the current is blocked by -conotoxin GVIA (CGVIA) (Jones and Jacobs, 1990;Elmslie et al, 1992). Therefore, these neurons should be an ideal preparation to study single N-channels and have been used in previous studies (Lipscombe et al, 1989;.…”

Section: Abstract: N-type Calcium Channels; L-type Calcium Channels;mentioning

confidence: 99%

Identification of the Single Channels that Underlie the N-Type and L-Type Calcium Currents in Bullfrog Sympathetic Neurons

Elmslie

1997

J. Neurosci.

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Most of the whole-cell calcium current of frog sympathetic neurons is an N-type current, blocked by -conotoxin GVIA (CGVIA). Thus, these cells should be an excellent system to study the properties of single N-type channels. However, a channel that is active near Ϫ10 mV in isotonic Ba 2ϩ , originally identified as "N-type," corresponds more closely to a CGVIAresistant component of the whole-cell current observed in 100 mM Ba 2ϩ . That conclusion would imply that the true singlechannel correlate of the macroscopic N-current remains to be identified in frog sympathetic neurons. I report here recordings from cell-attached patches of a calcium channel that activates in the appropriate voltage range (Ͼ0 mV, in isotonic Ba 2ϩ ) and is blocked by CGVIA. This channel has a slope conductance of 20 pS (range, 17-25 pS) and a single-channel current of Ϫ1.3 pA at 0 mV. Other channels active in the same voltage range (24 pS, Ϫ1.3 pA at 0 mV) were identified as L-type channels because they exhibited long openings after repolarization in the presence of 1 M Bay K 8644 and were resistant to CGVIA. A third channel type (13-19 pS) was distinguished by current amplitude (Ϫ0.6 pA at 0 mV) and strong inactivation at Ϫ40 mV. The similarity in slope conductance among these channels demonstrates that distinguishing them requires the consideration of additional properties. The CGVIA-sensitive channel can be identified as an N-type calcium channel.

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Dihydropyridine actions on calcium currents of frog sympathetic neurons

Cited by 102 publications

References 30 publications

Direct Measurements of Presynaptic Calcium and Calcium-Activated Potassium Currents Regulating Neurotransmitter Release at CulturedXenopusNerve–Muscle Synapses

Direct Measurements of Presynaptic Calcium and Calcium-Activated Potassium Currents Regulating Neurotransmitter Release at CulturedXenopusNerve–Muscle Synapses

Enhanced expression of Ca2+ channels by nerve growth factor and the v‐src oncogene in rat phaeochromocytoma cells.

Identification of the Single Channels that Underlie the N-Type and L-Type Calcium Currents in Bullfrog Sympathetic Neurons

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