Isoprenaline-stimulated differential adrenergic response of K+ channels in skeletal muscle under hypokalaemic conditions

Foppen, R.J. Geukes; Heukelom, J. Siegenbeek van

doi:10.1007/s00424-003-1042-y

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…For example, intra-arterial infusion of epinephrine provoked attacks of weakness in a HypoPP patient (28), whereas in vitro studies of human Ca V 1.1 HypoPP fibers for which bulk external K + was clamped showed enhanced contractility when 1 μM epinephrine was added to fibers bathed in 4.5 mM K + , but triggered weakness in a 1 mM K + solution (19). These complexities illustrate the need to further dissect the effects of Na + /K + -ATPase stimulation, K + homeostasis, and other downstream events of adrenergic signaling, such as Ca 2+ -activated K + channel activation (29), with regard to regulation of excitability in HypoPP muscle. Our mouse model provides the opportunity to systematically explore these phenomena and identify potential therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis

Burns³

et al. 2011

J. Clin. Invest.

109

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Hypokalemic periodic paralysis (HypoPP) is an ion channelopathy of skeletal muscle characterized by attacks of muscle weakness associated with low serum K + . HypoPP results from a transient failure of muscle fiber excitability. Mutations in the genes encoding a calcium channel (Ca V 1.1) and a sodium channel (Na V 1.4) have been identified in HypoPP families. Mutations of Na V 1.4 give rise to a heterogeneous group of muscle disorders, with gain-of-function defects causing myotonia or hyperkalemic periodic paralysis. To address the question of specificity for the allele encoding the Na V 1.4-R669H variant as a cause of HypoPP and to produce a model system in which to characterize functional defects of the mutant channel and susceptibility to paralysis, we generated knockin mice carrying the ortholog of the gene encoding the Na V 1.4-R669H variant (referred to herein as R669H mice). Homozygous R669H mice had a robust HypoPP phenotype, with transient loss of muscle excitability and weakness in low-K + challenge, insensitivity to high-K + challenge, dominant inheritance, and absence of myotonia. Recovery was sensitive to the Na + /K + -ATPase pump inhibitor ouabain. Affected fibers had an anomalous inward current at hyperpolarized potentials, consistent with the proposal that a leaky gating pore in R669H channels triggers attacks, whereas a reduction in the amplitude of action potentials implies additional loss-of-function changes for the mutant Na V 1.4 channels.

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Section: Discussionmentioning

confidence: 99%

A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis

Burns³

et al. 2011

J. Clin. Invest.

109

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“…Faster processes are also mediated via β 2 -receptors. They decrease muscle excitability by closing inward rectifying potassium channels, opening calcium-activated potassium channels [49] and blocking sodium currents [50]. In addition, because sympathetic activity produces rapid changes in blood flow to skeletal muscle, it has been argued that ischaemia (or its consequences e.g.…”

Section: Discussionmentioning

confidence: 99%

Beta-Adrenergic Modulation of Tremor and Corticomuscular Coherence in Humans

Baker

2012

PLoS ONE

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Coherence between the bioelectric activity of sensorimotor cortex and contralateral muscles can be observed around 20 Hz. By contrast, physiological tremor has a dominant frequency around 10 Hz. Although tremor has multiple sources, it is partly central in origin, reflecting a component of motoneuron discharge at this frequency. The motoneuron response to ∼20 Hz descending input could be altered by non-linear interactions with ∼10 Hz motoneuron firing. We investigated this further in eight healthy human subjects by testing the effects of the beta-adrenergic agents propranolol (non-selective β-antagonist) and salbutamol (β2-agonist), which are known to alter the size of physiological tremor. Corticomuscular coherence was assessed during an auxotonic precision grip task; tremor was quantified using accelerometry during index finger extension. Experiments with propranolol used a double-blind, placebo-controlled crossover design. A single oral dose of propranolol (40 mg) significantly increased beta band (15.3–32.2 Hz) corticomuscular coherence compared with placebo, but reduced tremor in the 6.2–11.9 Hz range. Salbutamol (2.5 mg) was administered by inhalation. Whilst salbutamol significantly increased tremor amplitude as expected, it did not change corticomuscular coherence. The opposite direction of the effects of propranolol on corticomuscular coherence and tremor, and the fact that salbutamol enhances tremor but does not affect coherence, implies that the magnitude of corticomuscular coherence is little influenced by non-linear interactions with 10 Hz oscillations in motoneurons or the periphery. Instead, we suggest that propranolol and salbutamol may affect both tremor and corticomuscular coherence partly via a central site of action.

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“…V m changes can be induced by [K + ] o variations [16,18,19,22]. Due to the dominant P Cl , [K + ] o variations will be accompanied by changes in [Cl − ] i [1,2].…”

Section: Potassium Variationsmentioning

confidence: 98%

“…For example, binding of Ba 2+ to IRK occurs within 20-200 ms of the ion's presentation [3,29,36], and membrane resistance increases within 30 s [25], but actual membrane depolarization requires several minutes [7,10,15,19,25,37]. While in principle, such discrepancies could result from the absence or inactivity of IRK under the special conditions of the different experiments, that notion has been ruled out by single-cell measurements via the cell-attached patch procedure, where single IRK channel activity was recorded, and their blockade was compared with changes of the background cellular current [16].…”

Section: Introductionmentioning

confidence: 99%

“…The resting membrane potential (V m ) is thereby set close to the Nernst potential for potassium (E K ) [24] to ensure cellular excitability [21], and conditions which reduce IRK opening depolarize the muscle fiber [16]. In special circumstances, reduction of extracellular potassium concentration ([K + ] o ) has this effect [16,18,37,43], as does the extracellular application of IRK-channel blockers, such as Ba 2+ or Cs + [3,21,29,30,36,40].…”

Section: Introductionmentioning

confidence: 99%

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In skeletal muscle the relaxation of the resting membrane potential induced by K+ permeability changes depends on Cl? transport

Foppen

2004

Pfl�gers Archiv European Journal of Physiology

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In resting skeletal muscle the potassium permeability is determined by the permeability of the inwardly potassium rectifier. Continuous resting membrane potential measurements are done to follow the relaxation of the membrane potential upon changes in potassium permeability. Inhibition of the inwardly potassium rectifier, by extracellular application of 80 microM Ba(2+), causes the cell to depolarize with mean time constants as follows: in control 127+/-7 s ( n=23), in the presence of bumetanide, as an inhibitor of the Na(+)/K(+)/2Cl(-) cotransporter, 182+/-23 s ( n=7), in hypertonic media (340 mosmol/kg) 90.4+/-5 s ( n=7) and in reduced chloride medium 64+/-8 s ( n=5). The depolarizing relaxation of the membrane potential induced by reduction of extracellular potassium produces similar results. These time constants are at least three orders of magnitude slower than the time constants reported in the literature for the inhibition of the inwardly potassium rectifier. Chloride transport affects the relaxation of the membrane potential. A further characterization of chloride transport is done by following the relaxation of the membrane potential upon application of chloride transport modulators. It is argued that the electroneutral cotransporter, for which a flux was preliminarily estimated of 13.4 pmol cm(-2) s(-1), has a considerable role in the processes related to the resting membrane potential.

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Isoprenaline-stimulated differential adrenergic response of K+ channels in skeletal muscle under hypokalaemic conditions

Cited by 9 publications

References 42 publications

A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis

A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis

Beta-Adrenergic Modulation of Tremor and Corticomuscular Coherence in Humans

In skeletal muscle the relaxation of the resting membrane potential induced by K+ permeability changes depends on Cl? transport

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