A5061225503- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neural Engineering
- Genetic Neurodegenerative Diseases
- Lipid Membrane Structure and Behavior
- Muscle Physiology and Disorders
- Neuroscience and Neuropharmacology Research
- Electrochemical Analysis and Applications
- Chronic Lymphocytic Leukemia Research
- Neurogenetic and Muscular Disorders Research
- Photoreceptor and optogenetics research
- Muscle and Compartmental Disorders
- Neural dynamics and brain function
- Tissue Engineering and Regenerative Medicine
- Celiac Disease Research and Management
- Coordination Chemistry and Organometallics
- Ion Transport and Channel Regulation
- RNA regulation and disease
- HER2/EGFR in Cancer Research
- Olfactory and Sensory Function Studies
- Adipose Tissue and Metabolism
- Autoimmune Neurological Disorders and Treatments
- Electroconvulsive Therapy Studies
- Nanopore and Nanochannel Transport Studies
University of South Australia
2006-2020
University of California, Davis
2011
The University of Adelaide
1969-2001
Universität Hamburg
1998
Flinders Medical Centre
1994
Australian Institute of Business
1974-1987
Saarland University
1975
1. The influence of Cl‐ concentration and pH on gating the skeletal muscle channel, ClC‐1, has been assessed using voltage‐clamp technique Sf‐9 insect cell Xenopus oocyte expression systems. 2. Hyperpolarization induces deactivating inward currents comprising a steady‐state component two exponentially decaying components, which faster is weakly voltage dependent slower strongly dependent. 3. Open probability (Po) kinetics depend external but not internal concentration. 4. A point mutation,...
A distinctive feature of the voltage-dependent chloride channels ClC-0 (the Torpedo electroplaque channel) and ClC-1 major skeletal muscle is that acts as a ligand to its own channel, regulating channel opening so controlling permeation species. We have now studied number foreign anions through using voltage-clamp techniques on Xenopus oocytes Sf9 cells expressing human (hClC-1) or rat (rClC-1) isoforms, respectively. From their effect gating, presented in this paper can be divided into...
Mutations in the ClC-1 muscle chloride channel cause either recessive or dominant myotonia congenita. Using a systematic screening procedure, we have now identified four novel missense mutations (V286A, F307S) and (V236L, G285E), analysed effect of these other recently described (A313T, I556N) on properties Xenopus oocyte expression system. V286A, F307S A313T displayed 'classical' phenotype: their voltage dependence was shifted towards positive potentials dominant-negative by significantly...
ClC-1 is a dimeric, double-pored chloride channel that present in skeletal muscle. Mutations of this can result the condition myotonia, muscle disorder involving increased stiffness. It has been shown dominant form myotonia often results from mutations affect so-called slow, or common, gating process channel. causing are seen to cluster at interface monomers. This study investigated role H, I, P, and Q helices, which lie on interface, as well G helix, situated immediately behind H I gating....
Soon after the glass micropipette was invented as a micro-tool for manipulation of single bacteria and microinjection microsurgery living cells, it seen to hold promise microelectrode stimulate individual cells electrically study electrical potentials in them. Initial successes accurate mechanistic explanations results were achieved giant plant 1920s. Long known surface activity nerves muscles only resolved at similar cellular level 1930s 1940s discovery nerve fibers development finer tipped...
1. In the present work we investigated dependence on temperature of ionic conductance and gating human muscle ClC-1 chloride channels, transiently expressed in embryonic kidney (HEK 293) cells. 2. At normal pH, currents deactivated at negative potentials with a double-exponential time course. The constants exponential components, corresponding to relaxations fast slow gates, were dependent Q(10) values approximately 3 4, respectively. Current amplitude increased increasing 1.6. 3. voltage...
Functionally, the dimeric human skeletal muscle chloride channel hClC-1 is characterized by two distinctive gating processes, fast (protopore) and slow (common) gating. Of these, common poorly understood, but extensive conformational rearrangement suspected. To examine this possibility, we used FRET (fluorescence resonance energy transfer) assessed effects of manipulating common-gating process. Closure gate was accompanied a separation C-termini, whereas, with opening, C-termini approached...
Gating of the skeletal muscle chloride channel (ClC‐1) is sensitive to extracellular pH. In this study, whole‐cell recording currents from wild‐type (WT) ClC‐1 and a mutant, R304E, expressed in Sf‐9 insect cell line was used investigate further nature pH‐sensitive residues. Extracellular Cd 2+ produced concentration‐dependent block WT with an IC 50 1.0 ± 0.1 m Hill coefficient 2.0 0.3. This external pH, reducing at low apparent p K 6.8 for proton binding 3.0 Anthracene‐9‐carboxylate (A‐9‐C)...
Using whole‐cell patch‐clamping and Sf‐9 cells expressing the rat skeletal muscle chloride channel, rClC‐1, cellular mechanism responsible for myotonic side effects of clofibrate derivatives was examined. RS‐(±) 2‐(4‐chlorophenoxy)propionic acid (RS‐(±) CPP) its S‐(−) enantiomer produced pronounced on ClC‐1 gating. Both compounds caused channels to deactivate more rapidly at hyperpolarizing potentials, which showed as a decrease in time constants both fast slow deactivating components whole...
1 Permeation of a range hydrophobic anions through the rat skeletal muscle chloride channel, rClC-1, expressed in Sf-9 (a Spodoptera frugiperda insect cell line) cells has been studied using whole-cell patch-clamp technique. 2 Bi-ionic reversal potentials measured with external application foreign gave following permeability sequence: Cl− (1) > benzoate (0·15) hexanoate (0·12) butyrate (0·09) propionate (0·047) x≈ formate (0·046). Anions larger moieties were more permeant, which suggested...
Two novel mutations of the human CLCN1 chloride channel gene, c.592C>G (p.L198V) and c.2255A>G (p.K752R), are described, occurring coincidentally in one myotonic patient. These individual a construct with both cDNA were transcribed expressed Xenopus oocytes where gating parameters extracted from currents recorded under voltage clamp. We found that p.L198V mutation has its major effects on common (or slow) gate channel, as do other dominant ClC-1 mutations, may therefore be causative...
Several studies on clinical practice for Duchenne muscular dystrophy (DMD) have been conducted in Western countries. However, there only a few similar Asia and Oceania. Here, we investigate the steroid therapy-related DMD among local experts. In 2015, expert survey Oceania to acquire information regarding patients with assess current cooperation of Asian Oceanian Myology Centre, neuromuscular disease research network.We obtained responses from 87 out 148 clinicians (62%) 13 countries...
Although hydropathy analysis of the skeletal muscle chloride channel protein, ClC-1, initially predicted 13 potential membrane spanning domains (D1 to D13), later topological studies have suggested that domain D4 is extracellular and D13, conserved in all eukaryotic ClC channels, located within extensive cytoplasmic tail makes up carboxyl terminus protein. We examined effect deleting D13 (ΔD13) function by removing final 72 (fs923X), 100 (fs895X), 125 (L869X), 398 (N596X), 420 (Q574X) amino...
Commonly used loop diuretics produce side effects in man which are similar to chemically induced myotonia. These have structural affinity with known myotonic agents. We observed EMG myotonia vivo leg muscles of rats treated intravenous frusemide. In the presence several different diuretics, rat isolated diaphragm, soleus and extensor digitorum longus as well frog sartorius typically contractions relaxation times up seconds. Intracellular recording action potentials from diuretic‐treated...
Our knowledge about ClC-1 muscle chloride channel gating, previously gained from single-channel recording and noise analysis, provides a theoretical basis for further analysis of macroscopic currents. In the present study, we propose simple method calculation open probabilities (<i>P</i><sub>o</sub>) fast slow gates relative amplitudes inward current components. With this method, investigated effects 2-(4-chlorophenoxy) propionic acid (CPP), drug known to produce myotonia in animals,...
Two outer membrane proteins of Aeromonas hydrophila A6, isolated in a one-step affinity chromatography process based on carbohydrate reactivity, were found to be pore-forming molecules artificial planar bilayer membranes. These carbohydrate-reactive (CROMPs; M(r)s, 40,000 and 43,000) subjected amino acid analysis. The profiles for these two almost identical. A partial protein sequence 14-amino-acid fragment the 40,000-Da revealed homology with porins Escherichia coli A. hydrophila. CROMPs...
Transition metals block the muscle Cl- channel ClC-1, which belongs to a large family of double-barreled channels and transporters. In Torpedo ClC-0, Zn2+ is closely related common gating mechanism that opens closes both pores simultaneously, mutation C212S, locks gate open, also eliminates block. however, previous results suggested independent gating, cysteine residues involved in binding are different positions those confer sensitivity on ClC-0. this work, we show ClC-1 faster at...