PMID- 11897856
OWN - NLM
STAT- MEDLINE
DCOM- 20020620
LR  - 20191210
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 539
IP  - Pt 3
DP  - 2002 Mar 15
TI  - Differential effects of sarcoplasmic reticular Ca(2+)-ATPase inhibition on charge 
      movements and calcium transients in intact amphibian skeletal muscle fibres.
PG  - 869-82
AB  - A hypothesis in which intramembrane charge reflects a voltage sensing process 
      allosterically coupled to transitions in ryanodine receptor (RyR)-Ca(2+) release 
      channels as opposed to one driven by release of intracellularly stored Ca(2+) 
      would predict that such charging phenomena should persist in skeletal muscle 
      fibres unable to release stored Ca(2+). Charge movement components were 
      accordingly investigated in intact voltage-clamped amphibian fibres treated with 
      known sarcoplasmic reticular (SR) Ca(2+)-ATPase inhibitors. Cyclopiazonic acid 
      (CPA) pretreatment abolished Ca(2+) transients in fluo-3-loaded fibres following 
      even prolonged applications of caffeine (10 mM) or K(+) (122 mM). Both CPA and 
      thapsigargin (TG) transformed charge movements that included delayed (q(gamma)) 
      "hump" components into simpler decays. However, steady-state charge-voltage 
      characteristics were conserved to values (maximum charge, Q(max) approximately 
      equal to 20-25 nC microF(-1); transition voltage, V* approximately equal to -40 
      to-50 mV; steepness factor, k approximately equal to 6-9 mV; holding voltage -90 
      mV) indicating persistent q(gamma) charge. The features of charge inactivation 
      similarly suggested persistent q(beta) and q(gamma) charge contributions in 
      CPA-treated fibres. Perchlorate (8.0 mM) restored the delayed kinetics shown by 
      "on" q(gamma) charge movements, prolonged their "off" decays, conserved both 
      Q(max) and k, yet failed to restore the capacity of such CPA-treated fibres for 
      Ca(2+) release. Introduction of perchlorate (8.0 mM) or caffeine (0.2 mM) to 
      tetracaine (2.0 mM)-treated fibres, also known to restore q(gamma) charge, 
      similarly failed to restore Ca(2+) transients. Steady-state intramembrane 
      q(gamma) charge thus persists with modified kinetics that can be restored to its 
      normally complex waveform by perchlorate, even in intact muscle fibres unable to 
      release Ca(2+). It is thus unlikely that q(gamma) charge movement is a 
      consequence of SR Ca(2+) release rather than changes in tubular membrane 
      potential.
FAU - Chawla, Sangeeta
AU  - Chawla S
AD  - Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 
      3EG, UK.
FAU - Skepper, Jeremy N
AU  - Skepper JN
FAU - Huang, Christopher L-H
AU  - Huang CL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Perchlorates)
RN  - 0 (Sodium Compounds)
RN  - 3G6A5W338E (Caffeine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 97F4MTY3VA (sodium perchlorate)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - RWP5GA015D (Potassium)
RN  - SY7Q814VUP (Calcium)
RN  - X9TLY4580Z (cyclopiazonic acid)
SB  - IM
MH  - Animals
MH  - Caffeine/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors/*physiology
MH  - Cytosol/drug effects/metabolism
MH  - Electrophysiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Homeostasis/physiology
MH  - In Vitro Techniques
MH  - Indoles/pharmacology
MH  - Kinetics
MH  - Muscle Fibers, Skeletal/*metabolism
MH  - Muscle, Skeletal/*metabolism
MH  - Perchlorates/pharmacology
MH  - Potassium/pharmacology
MH  - Rana temporaria
MH  - Reaction Time/drug effects
MH  - Sarcoplasmic Reticulum/*enzymology
MH  - Sodium Compounds/pharmacology
MH  - *Thapsigargin/pharmacology
PMC - PMC2290190
EDAT- 2002/03/19 10:00
MHDA- 2002/06/21 10:01
PMCR- 2003/03/15
CRDT- 2002/03/19 10:00
PHST- 2002/03/19 10:00 [pubmed]
PHST- 2002/06/21 10:01 [medline]
PHST- 2002/03/19 10:00 [entrez]
PHST- 2003/03/15 00:00 [pmc-release]
AID - PHY_13095 [pii]
AID - 10.1113/jphysiol.2001.013095 [doi]
PST - ppublish
SO  - J Physiol. 2002 Mar 15;539(Pt 3):869-82. doi: 10.1113/jphysiol.2001.013095.