scholarly journals Antibody-mediated enhancement of calcium permeability in cardiac myocytes.

1988 ◽  
Vol 168 (6) ◽  
pp. 2105-2119 ◽  
Author(s):  
H P Schultheiss ◽  
U Kühl ◽  
I Janda ◽  
B Melzner ◽  
G Ulrich ◽  
...  

Our study shows that antibodies, specific to the ADP/ATP carrier of the inner mitochondrial membrane, crossreact with the cell surface of cardiac myocytes, where the calcium channel seems to be the antigenic determinant. The antibodies enhanced the calcium current and suppressed its inactivation. Affinity-purified antibodies (IgG) exhibit an acute cytotoxic effect, which required extracellular calcium and was prevented by calcium channel blockers. Our findings suggest that antibody-mediated cytotoxicity results secondary to calcium overload caused by enhanced cellular calcium permeability, requiring no complement-dependent process.

1998 ◽  
Vol 79 (4) ◽  
pp. 2070-2081 ◽  
Author(s):  
Laura M. Hurley ◽  
Katherine Graubard

Hurley, Laura M. and Katherine Graubard. Pharmacologically and functionally distinct calcium currents of stomatogastric neurons. J. Neurophysiol. 79: 2070–2081, 1998. Previous studies have suggested the presence of different types of calcium channels in different regions of stomatogastric neurons. We sought to pharmacologically separate these calcium channel types. We used two different preparations from different regions of stomatogastric neurons to screen a range of selective calcium channel blockers. The two preparations were isolated cell bodies in culture, in which calcium current was measured directly, and isolated neuromuscular junction, in which synaptic transmission was the indirect assay for presynaptic calcium influx. The selective blockers were two different dihydropyridines, ω-Agatoxin IVA, and ω-Conotoxin GVIA. Cultured cell bodies possessed both high-threshold calcium current and calcium-activated outward current, similar to intact neurons. The calcium current had transient and maintained components, but both components had the same voltage dependence of activation and inactivation. Dihydropyridines at ≥10 μM blocked both high-threshold calcium current and calcium-activated outward current. Nanomolar doses of ω-Agatoxin IVA did not block calcium current, but micromolar doses did. ω-Conotoxin GVIA did not block either current. In contrast, at the neuromuscular junction, dihydropyridines reduced the amplitude of postsynaptic potentials by only a modest amount, whereas ω-Agatoxin IVA at doses as low as 64 nM reduced the amplitude of postsynaptic potentials almost entirely. These effects were presynaptic. ω-Conotoxin GVIA did not change the amplitude of postsynaptic potentials. The different pharmacological profiles of the two isolated preparations suggest that there are at least two different types of calcium channel in stomatogastric neurons and that ω-Agatoxin IVA and dihydropridines can be used to pharmacologically distinguish them.


1988 ◽  
Vol 255 (4) ◽  
pp. H960-H964 ◽  
Author(s):  
M. Morad ◽  
N. W. Davies ◽  
G. Ulrich ◽  
H. P. Schultheiss

Antibodies previously described to inhibit specifically nucleotide transport (ADP-ATP carrier) of the inner mitochondrial membrane were found to bind specifically to the sarcolemma of the enzymatically isolated rat ventricular myocytes. In this communication, we report for the first time that a component of these antibodies enhanced the Ca2+ current in isolated cardiac myocytes and potentiated twitch tension in ventricular strips. Prolonged exposure of rat myocytes to large concentrations of antibodies caused spontaneous contractions, progressive cell deterioration, and death. Our results thus show that a component of antibodies against ADP-ATP carrier cross-reacts with cardiac sarcolemmal proteins enhancing the Ca2+ channel.


2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
D Siemen ◽  
Y Cheng ◽  
X Gu ◽  
P Bednarczyk ◽  
GG Haddad ◽  
...  

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