β-Adrenergic Stimulation Selectively Inhibits Long-Lasting L-Type Calcium Channel Facilitation in Hippocampal Pyramidal Neurons

Cloues, Robin K.; Tavalin, Steven J.; Marrion, Neil V.

doi:10.1523/jneurosci.17-17-06493.1997

Cited by 45 publications

(46 citation statements)

References 52 publications

(65 reference statements)

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“…The different kinetics of I AHP and sI AHP are most likely not due to different subunit compositions of the underlying SK channels, because all cloned SK channels characterized so far present a fast activation upon binding of Ca 2ϩ to constitutively associated calmodulin (33). The faster time course of I AHP might be closely related to the time course of the intracellular Ca 2ϩ change occurring during one or more action potentials (6,29,34), whereas the slow kinetics of sI AHP might be due to mobilization of Ca 2ϩ from intracellular stores (6), diffusion of Ca 2ϩ to the sAHP channels from remote sites of entry (19,35), or to delayed facilitation of L-type Ca 2ϩ channels (36). In a recent interesting study, a functional coupling has been proposed between SK channels and L-type calcium channels in hippocampal neurons (37).…”

Section: Resultsmentioning

confidence: 99%

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Stocker

Krause

Pedarzani

1999

Proc. Natl. Acad. Sci. U.S.A.

361

435

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In hippocampal and other cortical neurons, action potentials are followed by afterhyperpolarizations (AHPs) generated by the activation of small-conductance Ca 2؉ -activated K ؉ channels (SK channels). By shaping the neuronal firing pattern, these AHPs contribute to the regulation of excitability and to the encoding function of neurons. Here we report that CA1 pyramidal neurons express an AHP current that is suppressed by apamin and is involved in the control of repetitive firing. This current presents distinct kinetic and pharmacological features, and it is modulated differently than the apamin-insensitive slow AHP current. Furthermore, our in situ hybridizations show that the apaminsensitive SK subunits are expressed in CA1 pyramidal neurons, providing a potential molecular correlate to the apaminsensitive AHP current. Altogether, these results clarify the discrepancy between the reported high density of apaminbinding sites in the CA1 region and the apparent lack of an apamin-sensitive current in CA1 pyramidal neurons, and they may explain the effects of this toxin on hippocampal synaptic plasticity and learning.In many neurons of the central nervous system, action potentials are followed by a rise in intracellular Ca 2ϩ leading to a prolonged afterhyperpolarization (AHP) of the membrane (1-4). The currents underlying the AHP are mediated by small-conductance voltage-insensitive Ca 2ϩ -activated K ϩ channels (SK channels), and they can be classified into two groups on the basis of their kinetic and pharmacological properties (5): (i) I AHP is sensitive to the bee venom toxin apamin and presents a relatively fast activation and decay (6); (ii) sI AHP (where s stands for slow) is apamin insensitive, rises to peak and decays with time constants of several hundreds of milliseconds, and is modulated by many neurotransmitters (1, 4). Functionally, activation of I AHP controls the firing frequency in tonically spiking neurons, whereas activation of sI AHP leads to spike frequency adaptation (5). While most excitable cells present an apamin-sensitive I AHP , only a few nerve cells exhibit an apamin-insensitive sI AHP , or both types of currents (4, 5). In the hippocampus, electrophysiological experiments have so far shown a peculiar segregation of AHP currents in different types of neurons, with pyramidal neurons presenting exclusively sI AHP (1, 7), and oriens-alveus interneurons only I AHP (8). These results are in contrast with studies on the distribution of apamin-binding sites in rat brain sections, which show the highest density in the hippocampal CA1 region (9, 10).Three members of the SK family of K ϩ channels have recently been cloned (11). All of them are voltage-insensitive and activated by submicromolar intracellular Ca 2ϩ . Two of them, SK2 and SK3, are blocked by apamin, whereas SK1 is apamin insensitive (11). Given these features, the SK channel subunits cloned so far are likely to participate in the formation of native SK channels, giving rise to apamin-sensitive and -insensitive AHP currents i...

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Section: Resultsmentioning

confidence: 99%

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Stocker

Krause

Pedarzani

1999

Proc. Natl. Acad. Sci. U.S.A.

361

435

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“…Secretion has previously been shown to be mediated by releasing a competent excitosome complex assembled by VGCC and synaptic proteins (32, 34 -36, 38, 39, 56 -61). The frequent channel opening induced by BayK and FPL (17,18) implies potentially more interactive channels, frequent encounters of the channel with synaptic proteins, and generation of more competent releasing complexes (35,36,38,57,60,61). Therefore, the increase in the frequency of channel opening by BayK and FPL could have accounted in part for the increase in the rate of secretion observed in all the cations.…”

Section: Discussionmentioning

confidence: 99%

“…BayK, FPL, and CGP 48506, which are structurally unrelated, interact with the cardiac Cav1.2 channel through binding within discrete sites at the transmembrane and extracellular loops of the ␣ 1 1.2 pore-forming subunit (10 -14). BayK enhances macroscopic currents (15) by increasing the rate of transition to "mode 2" single channel behavior (16,17) and the single channel currents by means of lengthening the channel open time (17)(18)(19)(20). BayK binding at selective Cav1.2 regions alters indirectly the selectivity filter, in turn affecting ion permeability (21).…”

mentioning

confidence: 99%

Conformational Changes Induced in Voltage-gated Calcium Channel Cav1.2 by BayK 8644 or FPL64176 Modify the Kinetics of Secretion Independently of Ca2+ Influx

Marom

Hagalili

Sebag

et al. 2010

Journal of Biological Chemistry

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The role of the L-type calcium channel (Cav1.2) as a molecular switch that triggers secretion prior to Ca 2؉ transport has previously been demonstrated in bovine chromaffin cells and rat pancreatic beta cells. Here, we examined the effect of specific Cav1.2 allosteric modulators, BayK 8644 (BayK) and FPL64176 (FPL), on the kinetics of catecholamine release, as monitored by amperometry in single bovine chromaffin cells. We show that 2 M BayK or 0.5 M FPL accelerates the rate of catecholamine secretion to a similar extent in the presence either of the permeable Ca 2؉ and Ba 2؉ or the impermeable charge carrier La 3؉ . These results suggest that structural rearrangements generated through the binding of BayK or FPL, by altering the channel activity, could affect depolarization-evoked secretion prior to cation transport. FPL also accelerated the rate of secretion mediated by a Ca 2؉ -impermeable channel made by replacing the wild type ␣ 1 1.2 subunit was replaced with the mutant ␣ 1 1.2/ L775P. Furthermore, BayK and FPL modified the kinetic parameters of the fusion pore formation, which represent the initial contact between the vesicle lumen and the extracellular medium. A direct link between the channel activity and evoked secretion lends additional support to the view that the voltagegated Ca 2؉ channels act as a signaling molecular switch, triggering secretion upstream to ion transport into the cell.The kinetic properties of voltage-gated Ca 2ϩ channels (VGCC) 2 are determined by the conformational changes induced at the channel during membrane depolarization. The kinetics of the L-type VGCC Cav1 is modulated also by allosteric agonists, which include BayK 8644 (BayK), a 1,4-dihydropyridine, FPL64176 (FPL), and CGP 48506 (1-9). BayK, FPL, and CGP 48506, which are structurally unrelated, interact with the cardiac Cav1.2 channel through binding within discrete sites at the transmembrane and extracellular loops of the ␣ 1 1.2 pore-forming subunit (10 -14). BayK enhances macroscopic currents (15) by increasing the rate of transition to "mode 2" single channel behavior (16,17) and the single channel currents by means of lengthening the channel open time (17)(18)(19)(20). BayK binding at selective Cav1.2 regions alters indirectly the selectivity filter, in turn affecting ion permeability (21). The changes observed in channel deactivation and inactivation are sensitive to the type of the cation used as the charge carrier (17).Like BayK 8644 (1), FPL is coupled to the cation binding at the selectivity filter of Cav1.1 acting as an allosteric regulator (22). In neonatal rat ventricular myocytes and rat ventricular cells, FPL enhances Ca 2ϩ influx and slows both the activation and the inactivation kinetics of the Cav1.2 (23). In isolated rat ventricular myocytes, FPL slowed the transition of the channel to a closed or inactivated state (24). In GH3 cells, FPL increased Cav1.2 current amplitude and shifted the current-voltage relationship to negative voltages (25). Single channel analysis showed that FPL increased both the...

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“…Second messenger-mediated responses typically exhibit latencies of Ͼ20 msec to the foot of the response (Sodickson and Bean, 1996). (4) The slow activation of sI AHP may be attributable to delayed facilitation of the calcium channels, which supply the calcium to activate sI AHP (Cloues et al, 1997;Marrion and Tavalin, 1998). This hypothesis requires that the K channels underlying sI AHP respond rapidly to changes in [Ca 2ϩ ] i .…”

Section: Discussionmentioning

confidence: 99%

Photolytic Manipulation of [Ca²⁺]_iReveals Slow Kinetics of Potassium Channels Underlying the Afterhyperpolarization in Hipppocampal Pyramidal Neurons

1999

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The identity of the potassium channel underlying the slow, apamin-insensitive component of the afterhyperpolarization current (sI AHP ) remains unknown. We studied sI AHP in CA1 pyramidal neurons using simultaneous whole-cell recording, calcium fluorescence imaging, and flash photolysis of caged compounds. Intracellular calcium concentration ([Ca 2ϩ ] i ) peaked earlier and decayed more rapidly than sI AHP . Loading cells with low concentrations of the calcium chelator EGTA slowed the activation and decay of sI AHP . In the presence of EGTA, intracellular calcium decayed with two time constants. When [Ca 2ϩ ] i was increased rapidly after photolysis of DMNitrophen, both apamin-sensitive and apamin-insensitive outward currents were activated. The apamin-sensitive current activated rapidly (Ͻ20 msec), whereas the apamin-insensitive current activated more slowly (180 msec). The apamininsensitive current was reduced by application of serotonin and carbachol, confirming that it was caused by sI AHP channels. When [Ca 2ϩ ] i was decreased rapidly via photolysis of diazo-2, the decay of sI AHP was similar to control (1.7 sec). All results could be reproduced by a model potassium channel gated by calcium, suggesting that the channels underlying sI AHP have intrinsically slow kinetics because of their high affinity for calcium.

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β-Adrenergic Stimulation Selectively Inhibits Long-Lasting L-Type Calcium Channel Facilitation in Hippocampal Pyramidal Neurons

Cited by 45 publications

References 52 publications

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Conformational Changes Induced in Voltage-gated Calcium Channel Cav1.2 by BayK 8644 or FPL64176 Modify the Kinetics of Secretion Independently of Ca2+ Influx

Photolytic Manipulation of [Ca²⁺]_iReveals Slow Kinetics of Potassium Channels Underlying the Afterhyperpolarization in Hipppocampal Pyramidal Neurons

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β-Adrenergic Stimulation Selectively Inhibits Long-Lasting L-Type Calcium Channel Facilitation in Hippocampal Pyramidal Neurons

Cited by 45 publications

References 52 publications

An apamin-sensitive Ca 2+ -activated K + current in hippocampal pyramidal neurons

An apamin-sensitive Ca 2+ -activated K + current in hippocampal pyramidal neurons

Conformational Changes Induced in Voltage-gated Calcium Channel Cav1.2 by BayK 8644 or FPL64176 Modify the Kinetics of Secretion Independently of Ca2+ Influx

Photolytic Manipulation of [Ca2+]iReveals Slow Kinetics of Potassium Channels Underlying the Afterhyperpolarization in Hipppocampal Pyramidal Neurons

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An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Photolytic Manipulation of [Ca²⁺]_iReveals Slow Kinetics of Potassium Channels Underlying the Afterhyperpolarization in Hipppocampal Pyramidal Neurons