Influence of Cell Isolation and Recording Technique on the Voltage Dependence of the Fast Cardiac Sodium Current of the Rat

Eickhorn, Roland; Drägert, Christian; Antoni, H.

doi:10.1006/jmcc.1994.1129

Cited by 13 publications

(8 citation statements)

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“…These pH e ‐dependent effects on the voltage dependence of activation were seen on a background of a time‐dependent hyperpolarization of the voltage dependence of channel gating often seen in whole‐cell recording (Eickhorn et al ., 1994). This effect likely contributed to an underestimation of the shift occurring under acidic conditions and overestimated the shift under basic conditions (Fig.…”

Section: Resultssupporting

confidence: 93%

Modulation of calcium currents in mouse ventral horn neurons by extracellular pH

Carlin¹

2005

Eur J of Neuroscience

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Neuronal activity has been shown to modulate the pH of the extracellular environment. Since neuronal circuits in the ventral horn of the spinal cord are highly active during patterned movements, and voltage-gated calcium channels play an important role in the production of spinal motoneuron output, the effects of changes in extracellular pH (pH(e)) on calcium currents in ventral horn neurons of the mouse spinal cord were examined. It is demonstrated that these channels are sensitive to modulation by pH(e). The amplitude of the current mediated by these channels increased as the pH(e) was elevated. The elevated pH(e) also led to a hyperpolarizing shift in the voltage dependence of both activation and inactivation. The opposite effects were seen for a decrease in pH(e). It was also noted that a decrease in pH(e) was associated with a faster inactivation of the current. It is concluded that voltage-gated calcium currents in ventral horn neurons are modulated by changes in pH(e), and that this modulation may play a physiologically important role in determining motoneuronal excitability during behaviors such as locomotion.

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Section: Resultssupporting

confidence: 93%

Modulation of calcium currents in mouse ventral horn neurons by extracellular pH

Carlin¹

2005

Eur J of Neuroscience

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“…This limitation was partially overcome by a modification of the cell-attached patch-clamp recording 42 , the loose patch clamp 21,22,43 . This technique has been used to measure ionic currents in multicellular cardiac preparations such as trabeculae and papillary muscle 44,45,46 . However, none of these reports was performed on an intact perfused heart during a physiological triggered AP.…”

Section: Discussionmentioning

confidence: 99%

Intact Heart Loose Patch Photolysis Reveals Ionic Current Kinetics During Ventricular Action Potentials

Ramos-Franco

Aguilar-Sánchez

Escobar

2016

Circulation Research

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Rationale Assessing the underlying ionic currents during a triggered action potential (AP) in intact perfused hearts offers the opportunity to link molecular mechanisms with pathophysiological problems in cardiovascular research. The developed Loose Patch Photolysis (LPP) technique can provide striking new insights into cardiac function at the whole heart level during health and disease. Objective To measure transmembrane ionic currents during an AP in order to determine how and when surface Ca2+ influx that triggers Ca2+ induced Ca2+ release (CICR) occurs and how Ca2+ activated conductances can contribute to the genesis of AP phase 2. Methods and Results LPP allows the measurement of transmembrane ionic currents in intact hearts. During a triggered AP, a voltage-dependent Ca2+ conductance was fractionally activated (dis-inhibited) by rapidly photo-degrading nifedipine, the Ca2+ channel blocker. The ionic currents during a mouse ventricular AP showed a fast early component and a slower late component. Pharmacological studies established that the molecular basis underlying the early component was driven by an influx of Ca2+ through the L-type channel, CaV 1.2. The late component was identified as a Na+-Ca2+ exchanger (NCX) current mediated by Ca2+ released from the sarcoplasmic reticulum (SR). Conclusions The novel LPP technique allowed the dissection of transmembrane ionic currents in the intact heart. We were able to determine that during an AP L-Type Ca2+ current contributes to phase 1 while NCX contributes to phase 2. In addition, LPP revealed that the influx of Ca2+ through L-type Ca2+ channels terminates due to voltage-dependent deactivation and not by Ca2+ dependent inactivation, as commonly believed.

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“…This observation suggests that loss of cytoskeletal components shifts inactivation gating in a depolarizing direction, a finding consistent with our hypothesis that sodium channel inactivation gating is hyperpolarized in CIM because it is more tightly associated with cytoskeletal components. However, acute disruption of cytoskeleton by pressure during formation of seals during patch clamp measurements has been found to trigger hyperpolarized shifts in the voltage dependent of Na V 1.4 and Na V 1.5 activation and fast inactivation [34-37]. Thus, while it is clear that changes in cytoskeleton can have profound effects on the voltage dependence of sodium channel gating, we currently do not know which changes in cytoskeleton will translate into changes in sodium channel gating.…”

Section: Discussionmentioning

confidence: 99%

Altered sodium channel-protein associations in critical illness myopathy

et al. 2012

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BackgroundDuring the acute phase of critical illness myopathy (CIM) there is inexcitability of skeletal muscle. In a rat model of CIM, muscle inexcitability is due to inactivation of sodium channels. A major contributor to this sodium channel inactivation is a hyperpolarized shift in the voltage dependence of sodium channel inactivation. The goal of the current study was to find a biochemical correlate of the hyperpolarized shift in sodium channel inactivation.MethodsThe rat model of CIM was generated by cutting the sciatic nerve and subsequent injections of dexamethasone for 7 days. Skeletal muscle membranes were prepared from gastrocnemius muscles, and purification and biochemical analyses carried out. Immunoprecipitations were performed with a pan-sodium channel antibody, and the resulting complexes probed in Western blots with various antibodies.ResultsWe carried out analyses of sodium channel glycosylation, phosphorylation, and association with other proteins. Although there was some loss of channel glycosylation in the disease, as assessed by size analysis of glycosylated and de-glycosylated protein in control and CIM samples, previous work by other investigators suggest that such loss would most likely shift channel inactivation gating in a depolarizing direction; thus such loss was viewed as compensatory rather than causative of the disease. A phosphorylation site at serine 487 was identified on the NaV 1.4 sodium channel α subunit, but there was no clear evidence of altered phosphorylation in the disease. Co-immunoprecipitation experiments carried out with a pan-sodium channel antibody confirmed that the sodium channel was associated with proteins of the dystrophin associated protein complex (DAPC). This complex differed between control and CIM samples. Syntrophin, dystrophin, and plectin associated strongly with sodium channels in both control and disease conditions, while β-dystroglycan and neuronal nitric oxide synthase (nNOS) associated strongly with the sodium channel only in CIM. Recording of action potentials revealed that denervated muscle in mice lacking nNOS was more excitable than control denervated muscle.ConclusionTaken together, these data suggest that the conformation/protein association of the sodium channel complex differs in control and critical illness myopathy muscle membranes; and suggest that nitric oxide signaling plays a role in development of muscle inexcitability.

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Influence of Cell Isolation and Recording Technique on the Voltage Dependence of the Fast Cardiac Sodium Current of the Rat

Cited by 13 publications

References 0 publications

Modulation of calcium currents in mouse ventral horn neurons by extracellular pH

Modulation of calcium currents in mouse ventral horn neurons by extracellular pH

Intact Heart Loose Patch Photolysis Reveals Ionic Current Kinetics During Ventricular Action Potentials

Altered sodium channel-protein associations in critical illness myopathy

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