Membrane Potential and Dihydropyridine Block of Calcium Channels in the Heart: Influence of Drug Ionization on Blocking Activity

1988 ◽  
pp. 81-91 ◽  
Author(s):  
R. S. Kass ◽  
J. P. Arena
Keyword(s):  
Membrane Potential ◽  
Calcium Channels ◽  
Blocking Activity

Angiotensin II and potassium activate different calcium entry mechanisms in rat adrenal glomerulosa cells

1989 ◽  
Vol 122 (1) ◽  
pp. 361-370 ◽  
Author(s):  
A. Spät ◽  
I. Balla ◽  
T. Balla ◽  
E. J. Cragoe ◽  
Gy. Hajnóczky ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Angiotensin Ii ◽  
Calcium Channels ◽  
Small Reduction ◽  
Nickel Ions ◽  
Ca Uptake ◽  
Voltage Dependent ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Isolated Rat

ABSTRACT Initial 45Ca uptake was measured in isolated rat glomerulosa cells. A small reduction in membrane potential produced by increasing the K+ concentration from 2 to 3·6 mmol/l stimulated 45Ca uptake by about 35%, while a bigger depolarization induced by 18·5 mmol K+/l increased the uptake by about 100%. Since Ca2+ influx was already activated at a calculated membrane potential below −70 mV, and was found to be sensitive to the dihydropyridine antagonist nifedipine (1 μmol/l), but insensitive to nickel ions (100 μmol/l), it does not meet the criteria established for T- or L-type voltage-dependent Ca2+ channels. Exposure of glomerulosa cells to angiotensin II (AII) for 10 min also enhanced the rate of 45Ca influx. The effect of AII was not sensitive to 1 μmol nifedipine/l, but was strongly inhibited by 5-(N-4-chlorobenzyl)-N-(2′,4′-dimethyl)benzamil (CBDMB, 30 μmol/l), an inhibitor of the Na+/Ca2+ antiporter. These observations suggest that during the sustained phase of stimulation with AII, a CBDMB-sensitive mechanism, rather than dihydropyridine-sensitive calcium channels, is involved in Ca2+ uptake in rat glomerulosa cells. The bulk Ca2+ influx did not correlate with aldosterone production; however, the maintained activity of different Ca2+ entry mechanisms seems to be essential for AII-induced aldosterone production. Journal of Endocrinology (1989) 122, 361–370

Membrane Potential and Calcium Channels in Arterial Smooth Muscle Cells

1989 ◽  
pp. 37-44
Author(s):  
Mark T. Nelson ◽  
Nicholas B. Standen ◽  
Joseph E. Brayden ◽  
Jennings F. Worley
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Calcium Channels ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Arterial Smooth Muscle Cells

Endogenous release of 5-HT modulates the plateau phase of NMDA-induced membrane potential oscillations in lamprey spinal neurons

2014 ◽  
Vol 112 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Di Wang ◽  
Sten Grillner ◽  
Peter Wallén
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Calcium Channels ◽  
Nmda Receptors ◽  
Plateau Phase ◽  
Spinal Neurons ◽  
Potential Oscillations ◽  
Voltage Dependent ◽  
Endogenous Release ◽  
Membrane Potential Oscillations

The lamprey central nervous system has been used extensively as a model system for investigating the networks underlying vertebrate motor behavior. The locomotor networks can be activated by application of glutamate agonists, such as N-methyl-D-aspartic acid (NMDA), to the isolated spinal cord preparation. Many spinal neurons are capable of generating pacemaker-like membrane potential oscillations upon activation of NMDA receptors. These oscillations rely on the voltage-dependent properties of NMDA receptors in interaction with voltage-dependent potassium and calcium-dependent potassium (KCa) channels, as well as low voltage-activated calcium channels. Upon membrane depolarization, influx of calcium will activate KCa channels, which in turn, will contribute to repolarization and termination of the depolarized phase. The appearance of the NMDA-induced oscillations varies markedly between spinal cord preparations; they may either have a pronounced, depolarized plateau phase or be characterized by a short-lasting depolarization lasting approximately 200–300 ms without a plateau. Both types of oscillations increase in frequency with increased concentrations of NMDA. Here, we characterize these two types of membrane potential oscillations and show that they depend on the level of endogenous release of 5-HT in the spinal cord preparations. In the lamprey, 5-HT acts to block voltage-dependent calcium channels and will thereby modulate the activity of KCa channels. When 5-HT antagonists were administered, the plateau-like oscillations were converted to the second type of oscillations lacking a plateau phase. Conversely, plateau-like oscillations can be induced or prolonged by 5-HT agonists. These properties are most likely of significance for the modulatory action of 5-HT on the spinal networks for locomotion.

NMDA-Induced Intrinsic Voltage Oscillations Depend on L-Type Calcium Channels in Spinal Motoneurons of Adult Turtles

1998 ◽  
Vol 80 (6) ◽  
pp. 3380-3382 ◽  
Author(s):  
P. A. Guertin ◽  
J. Hounsgaard
Keyword(s):  
Membrane Potential ◽  
Nmda Receptor ◽  
Calcium Channels ◽  
Rhythmic Activity ◽  
Nmda Receptor Antagonists ◽  
Spinal Motoneurons ◽  
Slice Preparation ◽  
Receptor Antagonists ◽  
Intrinsic Oscillation

Guertin, P. A. and J. Hounsgaard. NMDA-induced intrinsic voltage oscillations depend on L-type calcium channels in spinal motoneurons of adult turtles. J. Neurophysiol. 80: 3380–3382, 1998. In a slice preparation from adult turtles, bath-applied N-methyl-d-aspartate (NMDA) induced rhythmic activity in spinal motoneurons. The underlying intrinsic oscillation in membrane potential was revealed in the presence of tetrodotoxin (TTX). NMDA-induced rhythmicity, in the presence or absence of TTX, was abolished or reduced by NMDA receptor antagonists and by three different classes of antagonists for L-type calcium channels. It is suggested that both NMDA receptor channels and L-type calcium channels contribute to NMDA-induced intrinsic oscillations in mature spinal motoneurons.

Modulation of a subthreshold calcium current by the neuropeptide FMRFamide in Aplysia neuron R15

1988 ◽  
Vol 60 (5) ◽  
pp. 1728-1738 ◽  
Author(s):  
R. H. Kramer ◽  
E. S. Levitan ◽  
G. M. Carrow ◽  
I. B. Levitan
Keyword(s):  
Membrane Potential ◽  
Cyclic Amp ◽  
Calcium Channels ◽  
Calcium Current ◽  
Molecular Mechanisms ◽  
Chloride Ions ◽  
Egg Laying ◽  
Pacemaker Activity ◽  
Channel Blockers ◽  
Inward Current

1. The effect of the endogenous neuropeptide FMRFamide (Phe-Met-Arg-Phe-amide) on the Aplysia bursting pacemaker neuron R15 was studied. Brief local applications of FMRFamide, both on R15 somata in situ, and on R15 somata that were isolated and maintained in primary cell culture, cause a hyperpolarization of the membrane potential and a suppression of spontaneous bursting or beating pacemaker activity. 2. Two-electrode voltage-clamp experiments revealed that FMRFamide decreases the amplitude of an inward current, which activates with depolarization starting at a membrane potential less depolarized than the threshold for action potentials. Previous studies have established that this subthreshold inward current is carried by calcium and is essential for the generation of bursting pacemaker activity in Aplysia neurons. The effect of FMRFamide on the subthreshold inward current of R15 is blocked by divalent cation calcium channel blockers, such as cobalt and manganese, and is unaffected by changing the external concentration of potassium or chloride ions, or addition of blockers of the calcium-activated potassium current, such as external tetraethylammonium or internal EGTA. 3. The subthreshold calcium current of R15 is also decreased by dopamine and by an unidentified synaptic neurotransmitter. These substances mimic and occlude the action of FMRFamide on the subthreshold calcium current, suggesting that all three transmitters converge to affect the same population of calcium channels in neuron R15. 4. The subthreshold calcium current is enhanced by neurotransmitters that elevate cyclic AMP in R15, including serotonin, and the Aplysia neuropeptide egg-laying hormone (ELH). Likewise, the effect of FMRFamide on the subthreshold calcium current is enhanced by serotonin, ELH, and a cyclic AMP analog, suggesting that FMRFamide and cyclic AMP have antagonistic actions on the same population of calcium channels in neuron R15. 5. We conclude that the suppression of spontaneous bursting or beating pacemaker activity in neuron R15 by FMRFamide is due to a decrease in the subthreshold calcium current. The subthreshold calcium current in R15 is a common target for modulation by many different transmitters, acting via several distinct molecular mechanisms.

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