The Voltage Sensor of Skeletal Muscle Excitation-Contraction Coupling: A Comparison with Ca2+ Channels

Pizarro, Gonzalo; Brum, Gustavo; Fill, Michael; Fitts, Robert H.; Rodriguez, M.E.; Uribe, Ismael; Rı́os, Eduardo

doi:10.1007/978-3-642-73914-9_13

Cited by 24 publications

(30 citation statements)

References 40 publications

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“…With 13 and 0 15 nm of PN-200-110, another dihydropyridine derivative, these authors obtained a 50 % current block when they induced the current from a holding potential of -90 and -65 mV, respectively. Pizarro, Brum, Fill, Fitts, Rodriguez, Uribe & Rios (1988;see also Rios & Brum, 1987) measured intramembrane charge movements and Ca21 transients in cut fibres. In a Ca2+-free, Mg2+-containing solution, the Ca21 transient disappeared almost completely after the application of nifedipine (1 /M) while charge movements changed their polarity, indicating a transformation of the gating system into the inactivated state (Q1-> Q2).…”

Section: Compari8on With Former Resultsmentioning

confidence: 99%

The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres.

Neuhaus

Rosenthal

Lüttgau

1990

The Journal of Physiology

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SUMMARY1. The effects of dihydropyridine (DHP) derivatives on current through the slow Ca2+ channel and on isometric force were investigated in short toe muscle fibres of the frog (Rana temporaria). The experiments were performed under voltage-clamp conditions with two flexible internal microelectrodes.2. The non-chiral DHP derivative nifedipine was used mainly because it allowed control measurements after the inactivation of the drug with UV light.3. In a TEA sulphate solution containing 4 mM-free Ca2+, nifedipine (1 /l4M) caused no relevant alterations in the time course of successive contractures induced by depolarizing steps to 0 mV of 3-5 min duration followed by a restoration time at -90 mV of 1-5 min.4. When external Ca2+ was replaced by Mg2+, nifedipine caused a dose-dependent shortening of contractures. The effect reached saturation at about 50 % of shortening with 1-5 ,uM-nifedipine. In the absence of divalent cations and with Na+ being the only metallic cation in the solution, shortening became more pronounced and maximum force decreased.5. The application of 2 /sm-nifedipine to a Ca2+-free, Mg2+-containing solution shifted the voltage dependence of force inactivation by 5-10 mV to more negative potentials. 6. Force activation was facilitated by nifedipine. In the presence of 2 /iMnifedipine in a Ca2+-containing solution, threshold potentials (rheobase) as negative as -75 mV were measured under microscopical observation. UV irradiation shifted the threshold potential back to the normal value of about -50 mV.7. The slow Ca2+ inward current was blocked almost completely by 5/#M-nifedipine, even when induced from negative holding potentials (-90 to -

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Section: Compari8on With Former Resultsmentioning

confidence: 99%

The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres.

Neuhaus

Rosenthal

Lüttgau

1990

The Journal of Physiology

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“…Another possibility would be that all DHP receptors are structurally identical Ca2+ channel molecules which, however, exhibit a very small open-state probability even at large depolarization (Lamb & Walsh, 1987). A large fraction of intramembrane charge is sensitive to phenylalkylamines and dihydropyridines (Hui, Milton & Eisenberg, 1984;Lamb, 1986;Pizarro et al 1988;Feldmeyer et al 1990). …”

Section: Models For the Kinetic Behaviour Of The Channelsmentioning

confidence: 99%

“…In view of the hypothesis that the Ca2+ INTRODUCTION The major Ca2+ current in adult vertebrate skeletal muscle is a component with the pharmacological sensitivity of L-type currents, but showing extraordinarily slow voltage-dependent activation (Sanchez & Stefani, 1983). The protein exhibiting binding sites for Ca2+ channel antagonists, often simply called the dihydropyridine (DHP) receptor, has also been linked, in skeletal muscle, to the process of excitation-contraction (EC) coupling Tanabe, Takeshima, Mikami, Flockerzi, Takahashi, Kangawa, Kojimi, Matsuo, Hirose & Numa, 1987;Pizarro, Brum, Fill, Fitts, Rodriguez, Uribe & Rios, 1988). It has been proposed that at least some of the DHP receptors constitute the voltage sensors which receive the voltage change of the T-tubular membrane and initiate the transmission of information to the sarcoplasmic reticulum (SR) to cause release of stored Ca2+ ions.…”

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confidence: 99%

Fast gating kinetics of the slow Ca2+ current in cut skeletal muscle fibres of the frog.

Feldmeyer

Melzer

Pohl

et al. 1990

The Journal of Physiology

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SUMMARY1. Calcium currents and intramembrane charge movements were measured in cut twitch muscle fibres of the frog and the time course of activation of the current was studied using various conditioning pulse protocols.2. When a conditioning activation was produced by a depolarizing pulse which ended before inactivation occurred, a subsequent depolarization led to a faster onset of activation, indicating that the system had not completely returned to the initial state during the interval between the two pulses.3. The interval between conditioning and test pulse was varied at different subthreshold potentials to study the time course of restoring the steady-state conditions. Complete restoration required a waiting period of about 1 min at the holding potential of -80 mV due to a very slow process but partial recovery was reached within 100 ms. This initial recovery process was strongly voltage dependent and became considerably slower when the interval potential approached the threshold for current activation.4. Stepping to a roughly 10 mV subthreshold potential without applying a conditioning activation caused no change in the time course of the current produced by a subsequent test depolarization. Depolarizing just to the current threshold caused a slowly progressing acceleration of test current activation.5. The peak current-voltage relation in the fast gating regime caused by a conditioning activation coincided with the current-voltage relation measured under steady-state conditions, indicating not that a new channel population had become activated but that the same channels showed a different gating behaviour.6. Intramembrane charge movements measured in 2 mM-Cd2+ and tested at potentials between -40 and + 40 mV showed negligible changes when preceded by a strong depolarization. 7. We discuss several possible models which can explain the fact that the current is speeded up by a conditioning activation while the charge movements remain unchanged. It is possible that the fast voltage-dependent transition which becomes visible after conditioning pulses reflects a rapid conformational change of the Ca2+ channel molecule which also occurs during its normal gating mode but remains undetectable in terms of conductance. In view of the hypothesis that the Ca2+ channel molecule forms a voltage sensor for excitation-contraction coupling this fast MS 7918 348

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“…The changes have been explained by different variants of the voltage-modulated receptor concept. In analogy to the effects of local anesthetics on Na ϩ channels (21), the proposed models suggest preferential binding of PAA drugs to inactivated states of the voltage sensor (6,7,22). For frog fibers, Erdmann and Lüttgau (6) reported a change of V 0.5 of the voltage dependence of availability by Ϫ46 mV induced by 5 M (Ϫ)D888.…”

Section: Comparison With Previous Studies On Paa Action In Skeletal Mmentioning

confidence: 94%

“…By using voltage-clamp conditions, it could be demonstrated that the paralysis by D600 or by the higher-affinity PAA drug D888 was removed by hyperpolarizing the fiber membrane to potentials between Ϫ120 and Ϫ150 mV (5,6). These experiments revealed that the PAA-induced inhibition results from a concentrationdependent shift to more negative potentials of the steady-state voltage dependence of force availability, probably caused by a selective binding of the drug to the inactivated conformational state of the voltage sensor for Ca 2ϩ release (5,7,8). Voltage-dependent channels are hetero-oligomeric proteins containing several auxiliary subunits in addition to the poreforming ␣-subunits (9).…”

mentioning

confidence: 96%

The auxiliary subunit γ ₁ of the skeletal muscle L-type Ca ²⁺ channel is an endogenous Ca ²⁺ antagonist

Andronache

Ursu

Lehnert

et al. 2007

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

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Ca 2؉ channels play crucial roles in cellular signal transduction and are important targets of pharmacological agents. They are also associated with auxiliary subunits exhibiting functions that are still incompletely resolved. Skeletal muscle L-type Ca 2؉ channels (dihydropyridine receptors, DHPRs) are specialized for the remote voltage control of type 1 ryanodine receptors (RyR1) to release stored Ca 2؉ . The skeletal muscle-specific ␥ subunit of the DHPR (␥1) down-modulates availability by altering its steady state voltage dependence. The effect resembles the action of certain Ca 2؉ antagonistic drugs that are thought to stabilize inactivated states of the DHPR. In the present study we investigated the cross influence of ␥1 and Ca 2؉ antagonists by using wild-type (␥؉/؉) and ␥1 knockout (␥؊/؊) mice. We studied voltage-dependent gating of both L-type Ca 2؉ current and Ca 2؉ release and the allosteric modulation of drug binding. We found that 10 M diltiazem, a benzothiazepine drug, more than compensated for the reduction in high-affinity binding of the dihydropyridine agent isradipine caused by ␥1 elimination; 5 M devapamil [(؊)D888], a phenylalkylamine Ca 2؉ antagonist, approximately reversed the right-shifted voltage dependence of availability and the accelerated recovery kinetics of Ca 2؉ current and Ca 2؉ release. Moreover, the presence of ␥1 altered the effect of D888 on availability and strongly enhanced its impact on recovery kinetics demonstrating that ␥1 and the drug do not act independently of each other. We propose that the ␥1 subunit of the DHPR functions as an endogenous Ca 2؉ antagonist whose task may be to minimize Ca 2؉ entry and Ca 2؉ release under stress-induced conditions favoring plasmalemma depolarization.accessory subunits ͉ dihydropyridine receptor ͉ excitation-contraction coupling ͉ mouse skeletal muscle ͉ phenylalkylamine

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The Voltage Sensor of Skeletal Muscle Excitation-Contraction Coupling: A Comparison with Ca2+ Channels

Cited by 24 publications

References 40 publications

The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres.

The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres.

Fast gating kinetics of the slow Ca2+ current in cut skeletal muscle fibres of the frog.

The auxiliary subunit γ ₁ of the skeletal muscle L-type Ca ²⁺ channel is an endogenous Ca ²⁺ antagonist

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The Voltage Sensor of Skeletal Muscle Excitation-Contraction Coupling: A Comparison with Ca2+ Channels

Cited by 24 publications

References 40 publications

The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres.

The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres.

Fast gating kinetics of the slow Ca2+ current in cut skeletal muscle fibres of the frog.

The auxiliary subunit γ 1 of the skeletal muscle L-type Ca 2+ channel is an endogenous Ca 2+ antagonist

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The auxiliary subunit γ ₁ of the skeletal muscle L-type Ca ²⁺ channel is an endogenous Ca ²⁺ antagonist