1-20 of 31736
Save search
Follow your search
Access your saved searches in your account
Would you like to receive an alert when new items match your search?
Close Modal
Sort by
Journal Articles

A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations

Anthony L. Hessel, Katelyn M. Manross, Matthew M. Borkowski, Christopher D. Rand, Khoi Nguyen
Journal: Journal of General Physiology
Series: Contractile Function
J Gen Physiol (2026) 158 (2): e202513773.
https://doi.org/10.1085/jgp.202513773
Published: 28 January 2026
View article titled, A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations
Open the PDF for A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations in another window
Images
Muscle fiber permeabilization pipelines. (a) Skeletal or cardiac muscles are initially excised along with connective tissues into samples of up to 1 cm thickness and can be stored at −20°C/−80°C for extended periods or immediately permeabilized for experimentation. (b) The permeabilization process reduces the sarcolemma’s ability to isolate sarcomeres from the extracellular space. This, in turn, provides the experimenter access to the sarcoplasm via the diffusion of chemicals across the (remaining) sarcolemma. (c) These samples are then either further stored or loaded onto an experimental rig for mechanical testing.

Muscle fiber permeabilization pipelines. (a) Skeletal or cardiac muscles a...

in A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations > Journal of General Physiology
Published: 28 January 2026
Figure 1. Muscle fiber permeabilization pipelines. (a) Skeletal or cardiac muscles are initially excised along with connective tissues into samples of up to 1 cm thickness and can be stored at −20°C/−80°C for extended periods or immediately More about this image found in Muscle fiber permeabilization pipelines. (a) Skeletal or cardiac muscles a...
Images
Considerations for sample attachment. (a) The force transmission chain from the motor to the transducer includes both the muscle sample and the attachments. (b–f) Commonly used methods for attaching muscle samples to force transducers and the length motor.

Considerations for sample attachment. (a) The force transmission chain fro...

in A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations > Journal of General Physiology
Published: 28 January 2026
Figure 2. Considerations for sample attachment. (a) The force transmission chain from the motor to the transducer includes both the muscle sample and the attachments. (b–f) Commonly used methods for attaching muscle samples to force More about this image found in Considerations for sample attachment. (a) The force transmission chain fro...
Images
Small-angle X-ray scattering of muscles provides direct measurement of sarcomeric protein organization. Sarcomeres are highly ordered protein complexes that are pseudocrystalline in nature. (a) Synchrotron light sources produce high-powered X-rays that pass through muscle fibers to create diffraction patterns from their interaction with the sarcomere structures. (b) A representative diffraction pattern from rat tibialis anterior, permeabilized fiber bundle at rest. The structural properties of both thick (myosin) and thin (actin) filaments show up as reflections and layer lines along the meridional plane (perpendicular to the equatorial plane) and change in identifiable ways when the muscle is activated or under myopathies. (c and d) Geometric lattice planes and repeating periodic structures on the thick and thin filaments underlie the meridional and equatorial diffraction features.

Small-angle X-ray scattering of muscles provides direct measurement of sarc...

in A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations > Journal of General Physiology
Published: 28 January 2026
Figure 3. Small-angle X-ray scattering of muscles provides direct measurement of sarcomeric protein organization. Sarcomeres are highly ordered protein complexes that are pseudocrystalline in nature. (a) Synchrotron light sources produce More about this image found in Small-angle X-ray scattering of muscles provides direct measurement of sarc...
Journal Articles

The relationship between apparent potentiation and the magnitude of the control response

Joe Henry Steinbach, Gustav Akk
Journal: Journal of General Physiology
J Gen Physiol (2026) 158 (2): e202513894.
https://doi.org/10.1085/jgp.202513894
Published: 27 January 2026
View article titled, The relationship between apparent potentiation and the magnitude of the control response
Open the PDF for The relationship between apparent potentiation and the magnitude of the control response in another window
Images
Energetics, RR, and magnitude of the control response for a fully efficacious agonist co-applied with a positive allosteric modulator. (A) The graph shows free energy change provided by the modulator (ΔGM) that is required to triple the control response at different magnitudes of the control response (ECagonist). For a control response equal to or greater than one-third of maximal, the energy cannot be calculated, as that would require a probability of being active ≥1. The calculations were done using Eq. 5. (B) The relationship between the RR and ECagonist was calculated (Eq. 6), assuming the modulator contributes −1 kcal/mol of free energy change toward gating.

Energetics, RR, and magnitude of the control response for a fully efficacio...

in The relationship between apparent potentiation and the magnitude of the control response > Journal of General Physiology
Published: 27 January 2026
Figure 1. Energetics, RR, and magnitude of the control response for a fully efficacious agonist co-applied with a positive allosteric modulator. (A) The graph shows free energy change provided by the modulator (ΔGM) that is required to triple More about this image found in Energetics, RR, and magnitude of the control response for a fully efficacio...
Images
Energetics, RR, and magnitude of the control response for partial agonists co-applied with a positive allosteric modulator. (A) The graph shows the free energy change provided by the modulator (ΔGM) that is required to triple the control response at different magnitudes of the control response (ECagonist). The red dashed line describes the relationship for an agonist that at saturating concentration generates a response with a PA of 0.5. The blue dash-dotted line describes the relationship for an agonist that at saturating concentration generates a response with a PA of 0.25. The calculations were done using Eq. 7. (B) The relationships between the RRs and ECagonist were calculated (Eq. 8) for the partial agonists, assuming the modulator contributes −1 kcal/mol of free energy change toward gating. The black solid lines in both panels are reproduced from Fig. 1 and illustrate the relationship for a fully efficacious agonist (at EC100 PA = 1).

Energetics, RR, and magnitude of the control response for partial agonists ...

in The relationship between apparent potentiation and the magnitude of the control response > Journal of General Physiology
Published: 27 January 2026
Figure 2. Energetics, RR, and magnitude of the control response for partial agonists co-applied with a positive allosteric modulator. (A) The graph shows the free energy change provided by the modulator (ΔGM) that is required to triple the More about this image found in Energetics, RR, and magnitude of the control response for partial agonists ...
Images
Energetics, RR, and magnitude of the control response for agonists co-applied with a negative allosteric modulator. (A) The graph shows the free energy change provided by the inhibitor (ΔGM) that is required to halve the control response at different magnitudes of the control response (ECagonist). The black solid line describes the relationship for a fully efficacious agonist that at saturating concentration generates a response approaching a PA of 1. The red dashed line describes the relationship for an agonist that at saturating concentration generates a response with a PA of 0.5. The blue dash-dotted line describes the relationship for an agonist that at saturating concentration generates a response with a PA of 0.25. The calculations were done using Eq. 7. (B) The relationships between the RRs and ECagonist were calculated (Eq. 8) for the three agonists, assuming the modulator contributes 1 kcal/mol of free energy change.

Energetics, RR, and magnitude of the control response for agonists co-appli...

in The relationship between apparent potentiation and the magnitude of the control response > Journal of General Physiology
Published: 27 January 2026
Figure 3. Energetics, RR, and magnitude of the control response for agonists co-applied with a negative allosteric modulator. (A) The graph shows the free energy change provided by the inhibitor (ΔGM) that is required to halve the control More about this image found in Energetics, RR, and magnitude of the control response for agonists co-appli...
Journal Articles

Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944

Jinglang Sun, Juan de la Rosa Vázquez, Adriana Hernández-González, Vladimir Yarov-Yarovoy, Amy Lee
Journal: Journal of General Physiology
J Gen Physiol (2026) 158 (2): e202513879.
https://doi.org/10.1085/jgp.202513879
Published: 05 January 2026
View article titled, Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944
Open the PDF for Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 in another window
Includes: Supplementary data
Images
Inhibition of CaV3.2 by Z944 and ML218. (A) Representative traces for CaV3.2 ICa elicited by 200-ms test pulses from Vhold of −90 to −20 mV before and after exposure to Z944. (B) Time course of ICa treated with vehicle and increasing concentrations of Z944. ICanorm represents current amplitude normalized to that measured during vehicle application. Points represented mean ± SEM. (C) For data in B, the inhibition (%) of ICa was plotted as a function of Z944 concentration and fit by nonlinear regression. (D) Representative I–V relationship for ICa before and after exposure to Z944. ICa was evoked by 200-ms test pulses from −90 mV. (E) Boltzmann fits of I–V relationships of averaged data obtained as in D were normalized to the peak ICa. (F–J) Same as A–E but with ML218. Parentheses indicate numbers of cells.

Inhibition of Ca V 3.2 by Z944 and ML218. (A) Representative ...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 1. Inhibition of Ca V 3.2 by Z944 and ML218. (A) Representative traces for CaV3.2 ICa elicited by 200-ms test pulses from Vhold of −90 to −20 mV before and after exposure to Z944. (B) Time course of ICa treated with vehicle and More about this image found in Inhibition of Ca V 3.2 by Z944 and ML218. (A) Representative ...
Images
Inhibition of CaV1.4 by Z944. (A) Left: Representative traces for CaV1.4 ICa elicited by 200-ms test pulses from a Vhold of −90 to +10 mV before and after exposure to Z944. Right: ICa traces (normalized to vehicle treated) show little to no inactivation with Z944. (B) Left: Time course of ICa treated with vehicle and increasing concentrations of Z944. ICanorm represents current amplitude normalized to that measured during vehicle application. Points represent mean ± SEM. Right: For data in B, inhibition (%, normalized to ICa during vehicle application) was plotted as a function of Z944 concentration and fit by nonlinear regression. Dashed line represents curve fit of data for CaV3.2 (Fig. 1 B). (C) Left: Representative I–V relationship for ICa before and after exposure to Z944. ICa was evoked by 200-ms test pulses from −90 mV. Right: Boltzmann fits of I–V relationships of averaged data were normalized to the peak ICa. (D) Peak current density (IPeak), Gmax, and Vh before and after exposure to Z944 (5 µM). P values were determined by paired t tests. In B and C, parentheses indicate numbers of cells.

Inhibition of Ca V 1.4 by Z944. (A) Left: Representative trac...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 2. Inhibition of Ca V 1.4 by Z944. (A) Left: Representative traces for CaV1.4 ICa elicited by 200-ms test pulses from a Vhold of −90 to +10 mV before and after exposure to Z944. Right: ICa traces (normalized to vehicle treated) show More about this image found in Inhibition of Ca V 1.4 by Z944. (A) Left: Representative trac...
Images
Inhibition of CaV1.4 by ML218. (A) Left: Representative traces for CaV1.4 ICa elicited by a 200-ms test pulse from −90 to +10 mV before and after exposure to ML218. Right: ICa traces (normalized to vehicle treated) show inactivation with ML218 at 10 and 100 μM. (B) Left: Time course of ICa treated with vehicle (control) or the indicated concentrations of ML218. ICanorm represents current amplitude normalized to that measured during vehicle application. Points represent mean ± SEM. Right, Dose–response plot showing the inhibition (%) of ICa as a function of ML218 concentration fit by nonlinear regression. Dashed line represents curve fit of data for CaV3.2 (Fig. 1 H). (C) Left: Representative I–V plot for ICa before and after exposure to ML218. ICa was evoked by 200-ms test pulses from −90 mV. Smooth lines represent Boltzmann fits. Right: Boltzmann fits of I–V data normalized to the peak ICa.(D) Peak current density (IPeak), normalized Gmax, and Vh before and after exposure to 5 μM ML218. P values were determined by paired t tests. In B and C, parentheses indicate numbers of cells.

Inhibition of Ca V 1.4 by ML218. (A) Left: Representative tra...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 3. Inhibition of Ca V 1.4 by ML218. (A) Left: Representative traces for CaV1.4 ICa elicited by a 200-ms test pulse from −90 to +10 mV before and after exposure to ML218. Right: ICa traces (normalized to vehicle treated) show More about this image found in Inhibition of Ca V 1.4 by ML218. (A) Left: Representative tra...
Images
Inhibition of CaV1.4 by ML218 is voltage independent. (A) Representative traces for CaV1.4 ICa elicited by a 200-ms test pulse from Vhold of −90 mV or −50 to +10 mV before and after exposure to ML218. (B) Representative I–V plots for ICa evoked by 50-ms test pulses from Vhold of −90 or −50 mV before and after exposure to ML218. Smooth lines represent Boltzmann fits. (C) Inhibition (%) and difference in Gmax (ΔGmax) caused by ML218 (5 µM). P values were determined by unpaired t tests.

Inhibition of Ca V 1.4 by ML218 is voltage independent. (A) R...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 4. Inhibition of Ca V 1.4 by ML218 is voltage independent. (A) Representative traces for CaV1.4 ICa elicited by a 200-ms test pulse from Vhold of −90 mV or −50 to +10 mV before and after exposure to ML218. (B) Representative I–V plots More about this image found in Inhibition of Ca V 1.4 by ML218 is voltage independent. (A) R...
Images
ML218 has similar effects on the CaV1.4 Δe47 variant that undergoes strong inactivation. (A and B) Representative I–V plots (A) and currents (B) for ICa evoked by 500-ms test pulses from Vhold of −90 mV before and after exposure to ML218 (50 nM). In A, smooth lines represent Boltzmann fits. In B, traces show effect of ML218 (50 nM) on current evoked by pulse to +10 mV. (C) Inhibition (%) and difference in Gmax (ΔGmax) caused by ML218 (50 nM). P values were determined by Mann–Whitney and unpaired t tests. (D) For data obtained as in A, fractional inactivation (fractional I) was measured as the amplitude of the current at the end of the pulse divided by the peak current amplitude and plotted against test voltage. (E) For currents in B, the trace obtained in the presence of ML218 was normalized to the trace for vehicle to illustrate the lack of effect of ML218 on enhancing inactivation.

ML218 has similar effects on the Ca V 1.4 Δe47 variant that un...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 5. ML218 has similar effects on the Ca V 1.4 Δe47 variant that undergoes strong inactivation. (A and B) Representative I–V plots (A) and currents (B) for ICa evoked by 500-ms test pulses from Vhold of −90 mV before and after exposure to More about this image found in ML218 has similar effects on the Ca V 1.4 Δe47 variant that un...
Images
Inhibition of CaV1.2 by ML218. (A) Left: Representative traces for CaV1.2 ICa before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 to 10 mV. Right: ICa traces (normalized to vehicle treated) show inactivation with ML218 at 10 and 100 μM. (B) Left: Time course of ICa treated with vehicle (control) or the indicated concentrations of ML218. ICanorm represents current amplitude normalized to that measured during vehicle application. Points represent mean ± SEM. Right: Dose–response plot showing the inhibition (%) of ICa as a function of ML218 concentration fit by nonlinear regression. Dashed line represents curve fit of data for CaV1.4 (Fig. 3 B). (C) Left: Representative I–V plot for ICa before and after exposure to ML218. ICa was evoked by 200-ms test pulses from −90 mV. Smooth lines represent Boltzmann fits. Right: Boltzmann fits of I–V data normalized to the peak ICa.(D) Peak current density (IPeak), normalized Gmax, and Vh before and after exposure to 5 μM ML218. P values were determined by paired t tests. In B and C, parentheses indicate numbers of cells.

Inhibition of Ca V 1.2 by ML218. (A) Left: Representative tra...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 6. Inhibition of Ca V 1.2 by ML218. (A) Left: Representative traces for CaV1.2 ICa before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 to 10 mV. Right: ICa traces (normalized to vehicle treated) show More about this image found in Inhibition of Ca V 1.2 by ML218. (A) Left: Representative tra...
Images
Effect of mutation of T1007Y on CaV1.4 inhibition by ISR. (A) Schematic showing CaV1.4 with four repeats (I–IV), each with six transmembrane helices (S1–S6) and a pore (P) loop. T1007Y mutation in IIIS5 is indicated (red circle). (B) Left: CaV1.4 WT ICa traces (normalized to vehicle treated) show inactivation with ISR. ICa was elicited by a 200-ms test pulse from −90 to 10 mV. Right: Representative ICa traces of CaV1.4 WT before and after exposure to ISR. ICa was elicited by a 50-ms test pulse from −90 mV to indicated voltages. (C) Left: Representative I–V plot for ICa before and after exposure to ISR. ICa was evoked by 50-ms test pulses from a Vhold of −90 mV. Smooth lines represent Boltzmann fits. Right: Boltzmann fits of I–V data normalized to the peak ICa (n = 3). (D and E) Same as B and C, but for CaV1.4 T1007Y.

Effect of mutation of T1007Y on Ca V 1.4 inhibition by ISR. (A...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 7. Effect of mutation of T1007Y on Ca V 1.4 inhibition by ISR. (A) Schematic showing CaV1.4 with four repeats (I–IV), each with six transmembrane helices (S1–S6) and a pore (P) loop. T1007Y mutation in IIIS5 is indicated (red circle). More about this image found in Effect of mutation of T1007Y on Ca V 1.4 inhibition by ISR. (A...
Images
Effect of T1007Y mutation on CaV1.4 inhibition by ML218. (A) Left: Representative CaV1.4 T1007Y ICa traces before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 mV to +10 mV. Right: ICa traces (normalized to vehicle treated) show inactivation with ML218 at 10 and 100 μM. (B) Left: Time course of ICa treated with vehicle (control) or the indicated concentrations of ML218. ICanorm represents current amplitude normalized to that measured during vehicle application. Points represent mean ± SEM. Right: Dose–response plot showing the inhibition (%) of ICa as a function of ML218 concentration fit by nonlinear regression. Dashed line represents curve fit of data for CaV1.4 WT (Fig. 3 B). (C) Left: Representative I–V plot for ICa before and after exposure to ML218. ICa was evoked by 200-ms test pulses from −90 mV. Smooth lines represent Boltzmann fits. Right: Boltzmann fits of I–V data normalized to the peak ICa. (D) Peak current density (IPeak), Gmax, and Vh before and after exposure to ML218 (5 µM). P values were determined by paired t tests. In B and C, parentheses indicate numbers of cells.

Effect of T1007Y mutation on Ca V 1.4 inhibition by ML218. (A)...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 8. Effect of T1007Y mutation on Ca V 1.4 inhibition by ML218. (A) Left: Representative CaV1.4 T1007Y ICa traces before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 mV to +10 mV. Right: ICa traces More about this image found in Effect of T1007Y mutation on Ca V 1.4 inhibition by ML218. (A)...
Images
Modeling of ML218 and Z944 in CaV1.4. (A) Structural overview of the CaV1.4 α1 subunit model generated by AF2, superimposed with experimental structures of nifedipine-bound rabbit CaV1.1 (PDB: 6jp5), ML218-bound CaV3.2 (PDB: 9ayk), and Z944-bound CaV3.1 (PDB: 6kzp). Boxed images show poses of ML218 and Z944 in the site corresponding to the CaV3-binding pocket in the II–III fenestration, nifedipine binding in the canonical DHP site, and the best docking pose of ML218 and Z944 in the III–IV fenestration. (B) Left panel: Top-down view of the CaV1.4 model, showing the positions of the ligands in experimental structures (nifedipine, ML218, and Z944). Middle and right panels: Best docking poses for ML218 and Z944 in the III–IV fenestration in CaV1.4, highlighting key interacting residues and hydrophobic surfaces (green shading). (C) Alignment of residues in IIIS5, IIIS6, and IVS6 in CaV3 and CaV1 subtypes. Residues involved in DHP binding are highlighted. Numbers correspond to human CaV1.4 sequence. ML218- and Z944-interacting methionine residues are in bold.

Modeling of ML218 and Z944 in Ca V 1.4. (A) Structural overvi...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 9. Modeling of ML218 and Z944 in Ca V 1.4. (A) Structural overview of the CaV1.4 α1 subunit model generated by AF2, superimposed with experimental structures of nifedipine-bound rabbit CaV1.1 (PDB: 6jp5 ), ML218-bound CaV3.2 (PDB: More about this image found in Modeling of ML218 and Z944 in Ca V 1.4. (A) Structural overvi...
Images
Effect of M1004A, M1129A, and M1426A mutations on CaV1.4 inhibition by ML218. (A–C) Left: Representative CaV1.4 mutant ICa traces before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 to +10 mV. Middle: Time course of ICa treated with vehicle (control) or the indicated concentrations of ML218. ICanorm represents current amplitude normalized to that measured during vehicle application. Points represent mean ± SEM. Right: Dose–response plot showing the inhibition (%) of ICa as a function of ML218 concentration fit by nonlinear regression. Dashed line represents curve fit of data for CaV1.4 WT (Fig. 3 B). Parentheses indicate numbers of cells. (D) Percentage of inhibition by ML218 (10 μM) of peak ICa measured in middle panels of A–C. Bars represent mean ± SEM, P value determined via Dunnett’s multiple comparisons test.

Effect of M1004A, M1129A, and M1426A mutations on Ca V 1.4 inh...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 10. Effect of M1004A, M1129A, and M1426A mutations on Ca V 1.4 inhibition by ML218. (A–C) Left: Representative CaV1.4 mutant ICa traces before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 to +10 mV. More about this image found in Effect of M1004A, M1129A, and M1426A mutations on Ca V 1.4 inh...
Images
Effect of V1063M mutation on ML218 inhibition of CaV1.2.(A) Left: Representative CaV1.2 V1063M ICa traces before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 mV to +10 mV. Right: Time course of ICa treated with vehicle (control) or the indicated concentrations of ML218. ICanorm represents current amplitude normalized to that measured during vehicle application. Points represent mean ± SEM. Parentheses indicate numbers of cells. (B) Dose–response plot showing the inhibition (%) of ICa as a function of ML218 concentration fit by nonlinear regression. Dashed line represents curve fit of data for CaV1.2 WT (Fig. 5 B). (C) Percentage of inhibition by ML218 (100 μM) of peak ICa measured in the time course panel of A. Bars represent mean ± SEM, P value determined via Dunnett’s multiple comparisons test.

Effect of V1063M mutation on ML218 inhibition of Ca V 1.2. (A...

in Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944 > Journal of General Physiology
Published: 05 January 2026
Figure 11. Effect of V1063M mutation on ML218 inhibition of Ca V 1.2. (A) Left: Representative CaV1.2 V1063M ICa traces before and after exposure to ML218. ICa was elicited by a 200-ms test pulse from −90 mV to +10 mV. Right: Time course of I More about this image found in Effect of V1063M mutation on ML218 inhibition of Ca V 1.2. (A...