Journal ArticleDOI
The agonist effect of dihydropyridines on Ca channels
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Measurements of single channel and whole cell cardiac Ca currents after application of two DHP agonists BAY K 8644 and CGP 28 392 show an increase in the probability that a single Ca channel, having opened and closed, will subsequently re-open during membrane depolarization.Abstract:
Dihydropyridines (DHP) have great potential for clinical use because of their inotropic and vasomotor effects. The mechanism of action is unknown although Ca currents have been implicated1,2. Here we report measurements of single channel and whole cell cardiac Ca currents after application of two DHP agonists BAY K 8644 and CGP 28 392. Whole cell Ca currents from individual myocytes were increased and the 50% effective doses (ED50) were similar to those reported for contractility in rabbit aorta and guinea pig heart1 and catecholamine release from cat adrenal glands3. The measured ED50 was also consistent with the apparent dissociation constant (Kd) of a high affinity binding site present in cardiac sarcolemmal vesicles4–7. We propose that the molecular basis for these results is an increase in the probability that a single Ca channel, having opened and closed, will subsequently re-open during membrane depolarization. At high concentrations of BAY K 8644 and in the presence of 96 mM Ba, different effects are observed, primarily a marked prolongation of open time8.read more
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Journal ArticleDOI
Three types of neuronal calcium channel with different calcium agonist sensitivity.
TL;DR: Evidence is reported for the coexistence of three types of Ca channel in sensory neurones of the chick dorsal root ganglion and the dihydropyridine Ca agonist Bay K 8644 strongly increases the opening probability of L-, but not T- or N-type channels.
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A novel type of cardiac calcium channel in ventricular cells.
TL;DR: A novel type of cardiac Ca channel with several properties that distinguish it from the hitherto-identified Ca channel in heart cells is described, which activates and inactivates at relatively negative potentials and remains functional long after patch excision.
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A G protein directly regulates mammalian cardiac calcium channels.
TL;DR: G proteins are now known to directly gate two classes of membrane ion channels, and in addition to regulating calcium channels indirectly through activation of cytoplasmic kinases, they can regulate calcium channels directly.
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Mechanisms of calcium channel modulation by β-adrenergic agents and dihydropyridine calcium agonists
TL;DR: Evidence is presented from fluctuation analysis of whole cell calcium current and unitary recordings of single calcium channel activity that contributes to the beta-adrenergic enhancement in frog, rat, and guinea-pig ventricular cells.
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Ion Channel Reconstitution
TL;DR: This chapter discusses the physical nature of Planar Bilayer Membrane Electrostatics and the Shapes of Channel Proteins, as well as analysis and Chemical Modification of Bacterial Porins.
References
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Journal ArticleDOI
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
TL;DR: The extracellular patch clamp method, which first allowed the detection of single channel currents in biological membranes, has been further refined to enable higher current resolution, direct membrane patch potential control, and physical isolation of membrane patches.
Journal ArticleDOI
Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels.
TL;DR: The properties of BAY K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate), one of the most potent of these novel compounds, are reported here.
Journal ArticleDOI
Sodium and calcium channels in bovine chromaffin cells
TL;DR: Inward currents in chromaffin cells were studied with the patch‐clamp technique and current recordings were obtained in cell‐attached, outside‐out and whole‐cell recording configurations.
Journal ArticleDOI
Calcium tolerant ventricular myocytes prepared by preincubation in a "KB medium".
Gerrit Isenberg,Udo Klöckner +1 more
TL;DR: It is discussed that both ageing and Ca intolerance of the un-conditioned cells result from Ca overload through the hyperpermeable membrane, and that Ca overload causes ATP depletion via mitochondrial disfunction and the constituents of the KB medium may act to prevent these processes.
Journal ArticleDOI
Electrical properties of individual cells isolated from adult rat ventricular myocardium.
TL;DR: It is concluded that the resting potential of these isolated cells is normally more negative than ‐70 mV, and that the cells retain the ionic mechanisms necessary for the generation of active currents.