Low single channel conductance of the major skeletal muscle chloride channel, ClC-1

Pusch, Michael; Steinmeyer, Klaus; Jentsch, Thomas J.

doi:10.1016/s0006-3495(94)80753-2

Cited by 134 publications

(98 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, several chloride channels (CLC; CLC-0, CLC-1, CLC-2, CLC-4, CLC-5, CLC-6, and CLC-7) cannot be detected in HEK293 as protein (by Western blotting), as mRNA (by RT-PCR), or functionally (by patch clamp) (3, 8, 9, 14-17, 24, 35, 37, 44, 45, 48). In addition, unit conductance, single-channel kinetics, and voltage dependence of these channels as well as CLC-3 are all different from the cryptdin channels we describe in this work (3,16,17,24,36,37,45). Thus all known members of the CLC family are unlikely candidates for activation by cryptdin 3 unless the peptide is capable of changing virtually every biophysical characteristic of the channel.…”

Section: Discussionmentioning

confidence: 69%

Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells

Yue

Merlin

Selsted

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Cryptdins are antimicrobial peptides secreted by Paneth cells located at the base of intestinal crypts. In addition to their antimicrobial function, cryptdins may also regulate salt and water secretion by intestinal epithelial cells. Recent work with short-circuit current measurements indicated that at least one cryptdin peptide, cryptdin 3, induces apical conductance(s) in Cl− secretory, including cystic fibrosis, epithelia. In the present study, we characterized the cryptdin 3-induced anion channel activity in human embryonic kidney (HEK) cells with single-channel patch-clamp techniques. The patch pipette was filled with solution containing different concentrations of cryptdin 3, and, after gigaseal formation, the channel activity was recorded with either cell-attached or inside-out patch modes. We found an anion selective channel with a conductance of 15 pS and open probability of 0.19, regardless of cryptdin 3 concentration. The mean open and closed times varied with the cryptdin 3 concentration. For cryptdin 3 concentrations of 10, 4, 1, and 0.5 μg/ml in the pipette, the corresponding mean open times were 1.2, 7.0, 9.0, and 17.4 ms and the corresponding mean closed times were 1.1, 1.6, 4.2, and 12.5 ms. These results suggest that cryptdin 3 forms anion-selective channels on the cytoplasmic membrane of HEK cells and that the kinetics of one such channel are affected by its interaction with other such channels.

show abstract

Section: Discussionmentioning

confidence: 69%

Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells

Yue

Merlin

Selsted

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Gating of ClC_1 is similar to the fast gating of ClC_0 in that it also activates with depolarization (Steinmeyer et al 1991;Pusch et al 1994;Rychkov et al 1996). Under normal conditions, ClC_1 lacks a slow hyperpolarization-activated gate.…”

Section: Resultsmentioning

confidence: 90%

Chloride dependence of hyperpolarization‐activated chloride channel gates

Pusch

Jordt

Stein

et al. 1999

The Journal of Physiology

116

View full text Add to dashboard Cite

The ClC gene family represents a class of voltage-dependent Cl¦ channels, with several members involved in human hereditary diseases (for review, see Jentsch, 1996;Thakker, 1997). Mutations in the muscular channel ClC_1 lead to dominant and recessive myotonia (Koch et al. 1992;Steinmeyer et al. 1994), mutations in ClC_5 lead to Dent's disease, a disorder associated with proteinuria, hypercalciuria and kidney stones (Lloyd et al. 1996), and mutations in ClC-Kb cause a certain form of Bartter's syndrome (Simon et al. 1997), a disease associated with renal salt wasting. The prototype ClC_0 Torpedo channel (Jentsch et al. 1990) is a dimer of two identical subunits (Ludewig et al. 1996;Middleton et al. 1996). It is a rather unusual 'doublebarrelled' channel in which each subunit probably forms an independent pore (Ludewig et al. 1996). A common slow gating process opens and closes both pores simultaneously. This produces the typical behaviour at the single channel level in which long closed periods are interrupted by bursts with two conductance states of equal size (Miller, 1982). The gating of an individual protopore appears to be completely independent from the gating state of the neighbouring pore once the slow gate is open (Ludewig et al. 1997c). The mechanism of the voltage dependence of ClC channels probably differs drastically from that found in typical voltage-dependent cation channels. The strong voltagedependent activation of Na¤ and K¤ channels is coupled to the movement of a charged segment of the channel protein (the S4-segment, Noda et al. 1984;St uhmer et al. 1989). No similar structure is present in ClC channels (Jentsch et al.

show abstract

“…The reduction of gCl, or more generally the concerted modulation of resting ionic conductance, via ANG II-induced activation of PKC and ROS signaling, may contribute to muscle fatigue and have an aggravating role in excitability disorders (23,29,43,72). This observation, along with the advancements in measuring ClC-1 currents by voltage-clamp recordings, paves the way for future studies of the ANG II effects on channel biophysics (25,28,48,60).…”

Section: Discussionmentioning

confidence: 94%

“…In spite of the important progress made in the last years in measuring ClC-1 chloride currents (25,28,48,60), macroscopic recordings of muscle gCl still provide crucial information about the function, pharmacology, and biochemical modulation of these channels in native skeletal muscle (8,19,20,22).…”

mentioning

confidence: 99%

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT₁ receptor and NADPH oxidase

Cozzoli

Liantonio

Conte

et al. 2014

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Cozzoli A, Liantonio A, Conte E, Cannone M, Massari AM, Giustino A, Scaramuzzi A, Pierno S, Mantuano P, Capogrosso RF, Camerino GM, De Luca A. Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT 1 receptor and NADPH oxidase. Am J Physiol Cell Physiol 307: C634 -C647, 2014. First published July 30, 2014; doi:10.1152/ajpcell.00372.2013.-Angiotensin II (ANG II) plays a role in muscle wasting and remodeling; however, little evidence shows its direct effects on specific muscle functions. We presently investigated the acute in vitro effects of ANG II on resting ionic conductance and calcium homeostasis of mouse extensor digitorum longus (EDL) muscle fibers, based on previous findings that in vivo inhibition of ANG II counteracts the impairment of macroscopic ClC-1 chloride channel conductance (gCl) in the mdx mouse model of muscular dystrophy. By means of intracellular microelectrode recordings we found that ANG II reduced gCl in the nanomolar range and in a concentration-dependent manner (EC 50 ϭ 0.06 M) meanwhile increasing potassium conductance (gK). Both effects were inhibited by the ANG II receptors type 1 (AT 1)-receptor antagonist losartan and the protein kinase C inhibitor chelerythrine; no antagonism was observed with the AT 2 antagonist PD123,319. The scavenger of reactive oxygen species (ROS) N-acetyl cysteine and the NADPH-oxidase (NOX) inhibitor apocynin also antagonized ANG II effects on resting ionic conductances; the ANG II-dependent gK increase was blocked by iberiotoxin, an inhibitor of calcium-activated potassium channels. ANG II also lowered the threshold for myofiber and muscle contraction. Both ANG II and the AT 1 agonist L162,313 increased the intracellular calcium transients, measured by fura-2, with a two-step pattern. These latter effects were not observed in the presence of losartan and of the phospholipase C inhibitor U73122 and the in absence of extracellular calcium, disclosing a G q-mediated calcium entry mechanism. The data show for the first time that the AT1-mediated ANG II pathway, also involving NOX and ROS, directly modulates ion channels and calcium homeostasis in adult myofibers.angiotensin II; chloride channel conductance; AT1 receptor; protein kinase C; NADPH oxidase IN FAST-TWITCH MUSCLE FIBERS, the macroscopic chloride conductance (gCl), due to the expression/activity of ClC-1 channel, accounts for ϳ80% of the total resting ionic conductance and ensures the electrical stability of myofibers (4, 9, 67, 68).In fact, the large gCl prevents membrane overexcitability due to potassium accumulation in transverse tubules during firing by reducing the length constant of electrotonic signal propagation (4, 9, 54). In spite of the important progress made in the last years in measuring ClC-1 chloride currents (25,28,48,60), macroscopic recordings of muscle gCl still provide crucial information about the function, pharmacology, and biochemical modulation of these channels in native skeletal muscle (8,19,20,22...

show abstract

Low single channel conductance of the major skeletal muscle chloride channel, ClC-1

Cited by 134 publications

References 33 publications

Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells

Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells

Chloride dependence of hyperpolarization‐activated chloride channel gates

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT₁ receptor and NADPH oxidase

Contact Info

Product

Resources

About

Low single channel conductance of the major skeletal muscle chloride channel, ClC-1

Cited by 134 publications

References 33 publications

Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells

Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells

Chloride dependence of hyperpolarization‐activated chloride channel gates

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase

Contact Info

Product

Resources

About

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT₁ receptor and NADPH oxidase