What question did this study set out to answer?

To elucidate the biophysical mechanisms, voltage dependence, and kinetic parameters of channel inhibition by ruthenium red and related tetraamine compounds on ryanodine-activated calcium release channels.

December 1, 1993The Journal of General PhysiologyOpen Access

Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle.

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Population

Ryanodine-activated Ca2+ release channel of skeletal muscle reconstituted in planar bilayers with…

Design

Preclinical

Authors

JMJianjie MaSociety of Critical Care Medicine

Discussion

Member takes

Implication

Characterizes voltage-dependent RyR pore block at single-channel level; leaves open translation to intact cardiac physiology or therapy.

Key Points

To elucidate the biophysical mechanisms, voltage dependence, and kinetic parameters of channel inhibition by ruthenium red and related tetraamine compounds on ryanodine-activated calcium release channels.
Reconstituted immunoaffinity-purified skeletal muscle ryanodine receptors into planar lipid bilayers.
Recorded single-channel currents at 2 kHz bandwidth across voltages from +60 to +100 mV following cis or trans addition of ruthenium red, tetraamine palladium (4APd), or tetraamine platinum (4APt).
Ruthenium red applied to the myoplasmic side produced a voltage-dependent flickery block on 500 pS channels, with dissociation constants (Kd) of 0.22 μM at +100 mV, 0.38 μM at +80 mV, and 0.62 μM at +60 mV, alongside a Hill coefficient near 2.
Channel blocking kinetics at +60 mV demonstrated an on-rate of 1.32 × 10^9 M^-1 s^-1 and an off-rate of 0.75 × 10^3 s^-1, with closing rates increasing linearly with blocker concentration while unblocking rates remained invariant.
Related compounds 4APd and 4APt blocked the channel with substantially lower affinities (Kd = 170 μM and 656 μM, respectively) and displayed Hill coefficients near 1.

Structured PICO

Population

Ryanodine-activated Ca2+ release channel of skeletal muscle reconstituted in planar bilayers with immunoaffinity purified ryanodine receptor

Intervention

Ruthenium red, tetraamine palladium (4APd), and tetraamine platinum (4APt)

Outcome

Channel blocking effect (half dissociation constants, Hill coefficients, on/off rates)surrogate

Ruthenium red blocks the ryanodine receptor by binding to multiple sites located in the conduction pore of the channel in a voltage-dependent manner.

Cite This Study

Jianjie Ma (1993) studied this question.

synapsesocial.com/papers/6a88f5ea3981116ebf4d262d https://doi.org/10.1085/jgp.102.6.1031

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Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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