Osmolality influences bistability of membrane potential under hypokalemic conditions in mouse skeletal muscle: an experimental and theoretical study

Foppen, R.J. Geukes; Mil, H.G.J. van; Heukelom, J. Siegenbeek van

doi:10.1016/s1095-6433(01)00430-5

Cited by 10 publications

(17 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4). Hysteresis is found when the contribution of the K IR dominates in P K [12,13] of unclamped cells, because its open-close kinetics depends on the K + gradient across the membrane [33,34]. These kinetic properties explain equally well the hysteresis loop we measured as well as the N-shaped i/V curve observed by others [4,10,40] during voltage-clamp experiments of cells with K IR in their membranes [34].…”

Section: Discussionsupporting

confidence: 65%

“…For comparison with lumbrical muscle, data obtained under identical conditions in soleus muscle are shown in the bottom two rows of Table 2. The fibres of the soleus also exhibited bistable behaviour at [K + ] o =0.76 mM: some cells depolarized, whereas others hyperpolarized [12,13,27]. Both the depolarized and the hyperpolarized soleus fibres became more negative when Iso was added, but the change was significantly smaller than in lumbrical fibres (Table 2).…”

Section: Influences That Vary the Magnitude Of The Iso Hyperpolarizationmentioning

confidence: 94%

“…The cellular K IR conductance is decreased in fibres from patients suffering from hypokalaemic periodic paralysis [30]. Treatment with Ba 2+ [12], a known K IR blocker [35], and hysteresis of V m [12,13] produce responses electrically similar to hypokalaemic periodic paralysis. Our results reveal differential responses of the important K + channels including the Ca 2+ sensitive BK channel.…”

Section: Hypokalaemic Periodic Paralysismentioning

confidence: 99%

See 2 more Smart Citations

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

Foppen

Heukelom

2003

Pflugers Arch - Eur J Physiol

Self Cite

View full text Add to dashboard Cite

The mechanism underlying the hyperpolarization induced by isoprenaline in mouse lumbrical muscle fibres was studied using cell-attached patch and intracellular membrane potential ( V(m)) recordings. Sarcolemmal inwardly rectifying K(+) channels (K(IR): 45 pS) and Ca(2+)-activated K(+) channels (BK: 181 pS) were identified. Exposure to isoprenaline closed K(IR) channels and increased BK channel activity. This increase was observed as a shift from 50 to -40 mV in the voltage dependence of channel activation. Isoprenaline prevented hysteresis of V(m) when the extracellular [K(+)] fell below 3.8 mM. This hysteresis was due to the properties of the K(IR). The effects of chloride transport and isoprenaline on V(m) did not interact purely competitively, but isoprenaline could prevent the depolarization induced by hyperosmotic media equally as well as bumetanide, which inhibits the Na(+)/K(+)/2Cl(-) cotransporter. In lumbrical muscle this leads to hyperpolarization, but this might vary among muscles. The switch from K(IR) to BK as the component of total K(+) conductance was due to isoprenaline.

show abstract

Section: Discussionsupporting

confidence: 65%

Section: Influences That Vary the Magnitude Of The Iso Hyperpolarizationmentioning

confidence: 94%

Section: Hypokalaemic Periodic Paralysismentioning

confidence: 99%

See 1 more Smart Citation

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

Foppen

Heukelom

2003

Pflugers Arch - Eur J Physiol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Reductions in extracellular K ϩ shift E K in a hyperpolarized direction, causing progressive decline in the IRK conductance because of its nonlinear reduced slope conductance at potentials depolarized from E K . 9,[17][18][19]48 Implicit in this hypothesis is the notion that a small conductance with a depolarizing influence (i.e., inward current at V REST ) antagonizes the IRK conductance. The K ϩ -dependent threshold for uncoupling V REST from E K and inducing depolarization is governed by the point at which the declining IRK conductance is insufficient to overcome the influence of this depolarizing inward current.…”

Section: Insights Into Resting Potential Abnormalities In Hypokalemicmentioning

confidence: 99%

Paradoxical depolarization of BA²⁺‐ treated muscle exposed to low extracellular K⁺: Insights into resting potential abnormalities in hypokalemic paralysis

Struyk

Cannon

2007

Muscle and Nerve

View full text Add to dashboard Cite

The combination of sarcolemmal depolarization and hypokalemia exhibited by the different forms of hypokalemic paralysis has been attributed to abnormalities of the K+ conductance governing the resting membrane potential (V(REST)). Supportive data have been observed in muscle fibers biopsied from patients with familial hypokalemic periodic paralysis (HypoPP) that paradoxically depolarize at low K+. Although this observation is consistent with anomalous K+ conductance, rigorous experimental support is lacking. To establish a foundation for understanding the pathophysiology of hypokalemic paralysis, we studied Ba2+-treated muscle fibers under voltage clamp. As anticipated, Ba2+ blocked inward rectifying K+ (IRK) currents, and thereby promoted depolarization, supporting the notion that the IRK conductance governs V(REST). The IRK conductance also declined when muscle was challenged with reduced external K+. When the external K+ declined below 1 mM, V(REST) became uncoupled from the K+ reversal potential and depolarized. Partial ( approximately 50%) block of the IRK conductance with Ba2+ potentiated this uncoupling threshold, such that depolarization could be elicited by exposure to 2 mM external K+. A quantitative computer model of resting ionic conductances was constructed, and simulations demonstrated that small alterations to resting conductances, such as adding a low-amplitude aberrant inward current flowing through "gating pores" in mutant Na+ channels causing HypoPP-2, can promote paradoxical depolarization in low K+. These findings offer a simple explanation for some of the heretofore poorly understood physiological abnormalities of HypoPP muscle and support the notion that pathological gating pore leakage currents may directly predispose to paralytic attacks.

show abstract

“…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%

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

View full text Add to dashboard Cite

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.

show abstract

Osmolality influences bistability of membrane potential under hypokalemic conditions in mouse skeletal muscle: an experimental and theoretical study

Cited by 10 publications

References 9 publications

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

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

Paradoxical depolarization of BA²⁺‐ treated muscle exposed to low extracellular K⁺: Insights into resting potential abnormalities in hypokalemic paralysis

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

Contact Info

Product

Resources

About

Osmolality influences bistability of membrane potential under hypokalemic conditions in mouse skeletal muscle: an experimental and theoretical study

Cited by 10 publications

References 9 publications

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

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

Paradoxical depolarization of BA2+‐ treated muscle exposed to low extracellular K+: Insights into resting potential abnormalities in hypokalemic paralysis

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

Contact Info

Product

Resources

About

Paradoxical depolarization of BA²⁺‐ treated muscle exposed to low extracellular K⁺: Insights into resting potential abnormalities in hypokalemic paralysis