Modal gating behavior of cardiac sodium channels in cell-free membrane patches

Nilius, Bernd

doi:10.1016/s0006-3495(88)83166-7

Cited by 91 publications

(71 citation statements)

References 19 publications

(15 reference statements)

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“…Modal changes in both activation and inactivation kinetics have been reported. The inactivation gating modes found for Na channels (Patlak and Ortiz, 1986;Nilius, 1988;Moorman et al, 1990;Zhou et al, 199 1) are somewhat similar to those found for N-type Ca2+ channels (Plummer and Hess,199 1; see Different Kinetic Patterns, above).…”

Section: Discussionsupporting

confidence: 61%

“…These include ligand-gated channels for glutamate (Patlak et al, 1979) and GABA (Macdonald and Twyman, 199 1) as well as voltage-gated channels such as Na channels (Patlak and Ortiz, 1986;Nilius, 1988;Moorman et al, 1990;Zhou et al, 1991) and Ca*+-activated K+ channels (Moczydlowski and Latorre, 1983;McManus and Magleby, 1988). Modal changes in both activation and inactivation kinetics have been reported.…”

Section: Discussionmentioning

confidence: 99%

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Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

1993

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In many neurons, N-type Ca2+ channels are a major Ca2+ entry pathway and strongly influence neurotransmitter release. We carried out cell- attached patch recordings (110 mM Ba2+ as charge carrier) to characterize the rapid opening and closing kinetics of N-type Ca2+ channel gating in frog sympathetic neurons. Single channels display at least three distinct patterns of gating, characterized as low-, medium- , and high-rho o modes on the basis of channel open probability (rho o) during depolarizing pulses to -10 mV. Spontaneous transitions from one mode to another are infrequent, with an exponential distribution of dwell times and mean sojourns of approximately 10 sec in each mode. Thus, a channel typically undergoes hundreds or thousands of open- closed transitions in one mode before switching to a different mode. Transitions between modes during a depolarization were occasionally detected, but were rare, as expected for infrequent modal switching. Within each mode, the activation kinetics were well described by a simple scheme (C2-C1-O), as previously reported for other types of Ca2+ channels. Rate constants are strikingly different from one mode to another, giving each mode its own characteristic kinetic signature. The gating behavior at -10 mV ranges from brief openings (approximately 0.3 msec) and long closures (10–20 msec) for low-rho o gating to long openings (3 msec) and brief closures (approximately 1 msec) for high- rho o gating. Intermediate values for mean open durations (approximately 1.5 msec) and mean closed durations (approximately 3 msec) were found for medium-rho o gating. In addition to being kinetically distinct, channel openings in the low-rho o mode often exhibit a unitary current approximately 0.2 pA larger than in the medium- or high-rho o mode. Each mode is characterized by its own voltage dependence: activation occurs at relatively negative potentials and is most steeply voltage dependent in the high-rho o mode, while activation requires very strong depolarizations and is weakly voltage dependent in the low-rho o mode. The proportion of time spent in the individual modes varies greatly from one patch to another, suggesting that modal gating may be subject to cellular control.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

1993

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“…Therefore, it appears to be different from the process underlying the SyPP. Alternatively, the situation may be similar to cardiac and skeletal muscle where a slow sodium current has been attributed to multiple re-openings of single classical sodium channels (Patlak & Ortiz, 1985Nilius, 1988;Josephson & Sperelakis, 1989). A third alternative G.-Y.…”

Section: Synaptic Prepotentials Elicited By Proximal and Distal Inputsmentioning

confidence: 99%

Synaptically triggered action potentials begin as a depolarizing ramp in rat hippocampal neurones in vitro.

Hvalby

Lacaille

et al. 1992

The Journal of Physiology

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SUMMARY1. During just-suprathreshold synaptic activation of CAI pyramidal cells in rat hippocampal slices in vitro the action potential begins as a slow depolarizing ramp, superimposed on the underlying EPSP and forming an integral part of the action potential. We call this ramp a synaptic prepotential (SyPP).2. In order to examine the SyPP, a procedure for subtraction of the underlying EPSP was necessary. Because action potentials were only elicited by a subset of EPSPs with larger than average amplitude, a subtraction of the mean subthreshold EPSP would not give valid results. Instead, an EPSP to be subtracted was selected from an assemblage of subthreshold EPSPs, so that its amplitude matched the initial part of the spike-generating EPSP.3. Virtually all action potentials started with a SyPP. Using an amplitude criterion of 1 S.D. of the mean of the matching subthreshold EPSPs, justsuprathreshold EPSPs gave prepotentials in 72-100 % of all action potentials from fifteen randomly selected cells. With a criterion of 2 S.D.S, the frequency of occurrence ranged from 36 to 100 %.4. With a constant stimulus strength, there was a certain variability of the spike latencies. Shorter latency spikes had steeper, but smaller SyPPs than later spikes, suggesting that the slope of SyPP influenced the timing of the cell discharge.5. The SyPP was best fitted by a single, exponentially rising curve, and was both smaller and slower than the large amplitude action potential. Its amplitude was 1-6 mV and the time constant 1-5 ms, which was 10-50 times slower than that of the upstroke of the action potential.6. A properly timed hyperpolarizing current pulse could block the large amplitude action potential, thereby unmasking the SyPP as an initial depolarizing ramp.7. The SyPP was more sensitive than the large amplitude action potential to intracellular injection of QX-314, a lidocaine derivative. At the concentrations. used

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“…It is noteworthy that most experiments on Na ϩ current properties in central neurons have been performed under conditions which might limit the exposure of channels to endogenous cytoplasmic factors. Often, Na ϩ channels are recorded in excised patches, which distances them from the cytoplasm and alters their kinetic and inactivation properties (12,13). Most cell-attached recordings have been from isolated cell preparations, which might be depleted of molecules released from nearby neurons and glia.…”

mentioning

confidence: 99%

Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na ⁺ channels

Fleidervish

Libman

Katz

et al. 2008

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

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Because the excitable properties of neurons in the neocortex depend on the characteristics of voltage-gated Na ؉ channels, factors which regulate those characteristics can fundamentally modify the dynamics of cortical circuits. Here, we report on a novel neuromodulatory mechanism that links the availability of Na ؉ channels to metabolism of polyamines (PAs) in the cerebral cortex. Using single channel and whole-cell recordings, we found that products of PA metabolism, the ubiquitous aliphatic polycations spermine and spermidine, are endogenous blockers of Na ؉ channels in layer 5 pyramidal cells. Because the blockade is activity-dependent, it is particularly effective against Na ؉ channels which fail to inactivate rapidly and thus underlie the persistent Na ؉ current. At the level of the local cortical circuit, pharmacological depletion of PAs led to increased spontaneous spiking and periods of hypersynchronous discharge. Our data suggest that changes in PA levels, whether associated with normal brain states or pathological conditions, profoundly modify Na ؉ channel availability and thereby shape the integrative behavior of single neurons and neocortical circuits.neocortex ͉ Layer 5 pyramidal neuron ͉ persistent sodium current ͉ sodium channel ͉ spermine

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Modal gating behavior of cardiac sodium channels in cell-free membrane patches

Cited by 91 publications

References 19 publications

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

Synaptically triggered action potentials begin as a depolarizing ramp in rat hippocampal neurones in vitro.

Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na ⁺ channels

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Modal gating behavior of cardiac sodium channels in cell-free membrane patches

Cited by 91 publications

References 19 publications

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

Synaptically triggered action potentials begin as a depolarizing ramp in rat hippocampal neurones in vitro.

Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na + channels

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Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na ⁺ channels