Mechanisms of inactivation of L-type calcium channels in human atrial myocytes

1997 ◽  
Vol 272 (4) ◽  
pp. H1625-H1635 ◽  
Author(s):  
H. Sun ◽  
N. Leblanc ◽  
S. Nattel
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Action Potential ◽  
Time Course ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes ◽  
Whole Cell Patch Clamp ◽  
Dependent Inactivation ◽  
Rapid Inactivation ◽  
Voltage Dependent ◽  
Ca2 Channels

We used whole cell patch-clamp and microfluorimetric (indo 1) techniques to measure Ca2+ current through L-type Ca2+ channels (I(Ca)) and Ca2+ transients in human atrial myocytes. During 1-s depolarizing pulses, I(Ca) inactivation was biexponential. The rate of rapid inactivation was slowed by ryanodine and was correlated with the rate of rise of cytoplasmic free Ca2+ concentration (r = 0.80, P < 0.01). Slower-phase I(Ca) inactivation was not affected by ryanodine but was accelerated by increasing the availability of Ca2+ to permeate the Ca2+ channel. Thus Ca2+ released from the sarcoplasmic reticulum (SR) was responsible for most I(Ca) inactivation during the first 50 ms of a depolarization to 0 mV, and thereafter inactivation by Ca2+ permeating the channel predominated. Pure voltage-dependent inactivation had a much slower time course of development (tau > 2 s) and played a smaller role than Ca2+-dependent mechanisms over a duration comparable to that of an action potential. We conclude that human atrial myocytes show both voltage- and Ca2+-dependent I(Ca) inactivation, that Ca2+-dependent mechanisms predominate over the time course of an action potential, and that although both Ca2+ released from the SR and Ca2+ permeating Ca2+ channels play a role, SR-released Ca2+ is particularly important in early, rapid I(Ca) inactivation, whereas Ca2+ permeating Ca2+ channels is more important in the slower phase of Ca2+-dependent inactivation.

Contribution of Na+/Ca2+ exchange to action potential of human atrial myocytes

1996 ◽  
Vol 271 (3) ◽  
pp. H1151-H1161 ◽  
Author(s):  
A. Benardeau ◽  
S. N. Hatem ◽  
C. Rucker-Martin ◽  
B. Le Grand ◽  
L. Mace ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Time Course ◽  
Significant Proportion ◽  
Type A ◽  
Plateau Phase ◽  
Type B ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes ◽  
Delayed Afterdepolarizations

The Ca2+ dye indo 1 was used to record internal Ca2+ (Cai) transients in order to investigate the role of the Na+/Ca2+ exchange current (INa/Ca) in whole cell patch-clamped human atrial myocytes After the activation of the L-type Ca2+ current by test pulses (20 ms) at +20 mV, a tail current (I(tail)) was activated at a holding potential of -80 mV with a density of -1.29 +/- 0.06 pA/pF. The time course of I(tail) followed that of Cai transients I(tail) was suppressed by dialyzing cells with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, applying 5 mM caffeine, or substituting external Na+ with Li+, indicating that this current was mainly generated by INa/Ca. Two types of action potential were recorded: type A, which is characterized by a narrow early plateau followed by a late low plateau phase, and type B, which is characterized by a small initial peak followed by a prolonged high plateau phase. Type B action potentials were found in larger cells than type A action potentials (membrane capacitance 81.8 +/- 4.5 and 122.4 +/- 7.0 pF in types A and B, respectively, P < 0.001). Substitution of external Na+ with Li+ shortened the late plateau of the type A action potential and the prolonged plateau of the type B action potential. Suppression of Cai transients by caffeine shortens the late part of both types of action potentials, whereas its lengthening effect on the initial phase of action potentials can result from several different mechanisms. The beat-to-beat dependent relationship between Cai transients and action potentials could be mediated by Ina/Ca- Delayed afterdepolarizations were present in a significant proportion of atrial myocytes in our experimental conditions. They were reversibly suppressed by Li+ substitution for Na+, suggesting that they are generated by INa/Ca. We conclude that INa/Ca plays a major role in the development of action potentials and delayed afterdepolarizations in isolated human atrial myocytes.

scholarly journals Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback.

1995 ◽  
Vol 105 (2) ◽  
pp. 209-226 ◽  
Author(s):  
A Zweifach ◽  
R S Lewis
Keyword(s):  
Time Course ◽  
Measurement Techniques ◽  
Fast Inactivation ◽  
Patch Clamp Recording ◽  
Crac Channels ◽  
Whole Cell Patch Clamp ◽  
Close Proximity ◽  
Rapid Inactivation ◽  
Voltage Dependent ◽  
Crac Channel

Rapid inactivation of Ca2+ release-activated Ca2+ (CRAC) channels was studied in Jurkat leukemic T lymphocytes using whole-cell patch clamp recording and [Ca2+]i measurement techniques. In the presence of 22 mM extracellular Ca2+, the Ca2+ current declined with a biexponential time course (time constants of 8-30 ms and 50-150 ms) during hyperpolarizing pulses to potentials more negative than -40 mV. Several lines of evidence suggest that the fast inactivation process is Ca2+ but not voltage dependent. First, the speed and extent of inactivation are enhanced by conditions that increase the rate of Ca2+ entry through open channels. Second, inactivation is substantially reduced when Ba2+ is present as the charge carrier. Third, inactivation is slowed by intracellular dialysis with BAPTA (12 mM), a rapid Ca2+ buffer, but not by raising the cytoplasmic concentration of EGTA, a slower chelator, from 1.2 to 12 mM. Recovery from fast inactivation is complete within 200 ms after repolarization to -12 mV. Rapid inactivation is unaffected by changes in the number of open CRAC channels or global [Ca2+]i. These results demonstrate that rapid inactivation of ICRAC results from the action of Ca2+ in close proximity to the intracellular mouths of individual channels, and that Ca2+ entry through one CRAC channel does not affect neighboring channels. A simple model for Ca2+ diffusion in the presence of a mobile buffer predicts multiple Ca2+ inactivation sites situated 3-4 nm from the intracellular mouth of the pore, consistent with a location on the CRAC channel itself.

scholarly journals A Complex of RIM2alpha and RIM-Binding Protein 2 Stabilizes Slow Voltage-Dependent Inactivation of Cochlear Inner Hair Cell Cav1.3 L-Type Ca2+ Channels

2018 ◽  
Vol 114 (3) ◽  
pp. 637a-638a
Author(s):  
Nadine J. Ortner ◽  
Alexandra Pinggera ◽  
Anita Siller ◽  
Nadja Hofer ◽  
Niels Brandt ◽  
...  
Keyword(s):  
Hair Cell ◽  
Binding Protein ◽  
Inner Hair Cell ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Ca2 Channels

Regulation of calcium current by voltage and cytoplasmic calcium in canine gastric smooth muscle

1992 ◽  
Vol 262 (3) ◽  
pp. C691-C700 ◽  
Author(s):  
F. Vogalis ◽  
N. G. Publicover ◽  
K. M. Sanders
Keyword(s):  
Time Course ◽  
Fast Component ◽  
Patch Clamp Technique ◽  
Similar Time ◽  
Whole Cell Patch Clamp ◽  
Gastric Smooth Muscle ◽  
Double Exponential ◽  
Circular Layer ◽  
Double Exponential Function ◽  
Ca2 Channels

The regulation of Ca2+ current by intracellular Ca2+ was studied in isolated myocytes from the circular layer of canine gastric antrum. Ca2+ current was measured with the whole cell patch-clamp technique, and changes in cytoplasmic Ca2+ ([Ca2+]i) were simultaneously measured with indo-1 fluorescence. Ca2+ currents were activated by depolarization and inactivated despite maintained depolarization. Ca2+ current inactivation was fit with a double exponential function. Using Ba2+ or Na+ as charge carriers removed the fast component of inactivation, whereas enhanced intracellular buffering of Ca2+ did not remove the fast component. Ca2+ currents were associated with a rise in [Ca2+]i. The decrease in [Ca2+]i following repolarization was exponential, and during the relaxation of [Ca2+]i, Ca2+ current was inactivated. The inward current recovered with a similar time course as the decrease in [Ca2+]i, suggesting that [Ca2+]i regulates the basal availability of Ca2+ channels. These data support the hypothesis that, although [Ca2+]i may influence the resting level of inactivation, it is the "submembrane" compartment of [Ca2+]i that regulates the development of inactivation.

Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes

1995 ◽  
Vol 268 (6) ◽  
pp. H2321-H2328 ◽  
Author(s):  
S. Zhang ◽  
T. Sawanobori ◽  
H. Adaniya ◽  
Y. Hirano ◽  
M. Hiraoka
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Decay Time ◽  
Action Potential Duration ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Membrane Surface ◽  
Surface Charges ◽  
Whole Cell Patch Clamp ◽  
K Current

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

scholarly journals Sarcoplasmic reticulum and L-type Ca2+channel activity regulate the beat-to-beat stability of calcium handling in human atrial myocytes

2011 ◽  
Vol 589 (13) ◽  
pp. 3247-3262 ◽  
Author(s):  
Anna Llach ◽  
Cristina E. Molina ◽  
Jacqueline Fernandes ◽  
Josep Padró ◽  
Juan Cinca ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Handling ◽  
Channel Activity ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes

scholarly journals Characteristic of the vasorlaxant action of the talatisamine alkaloid and its derivatives

2021 ◽  
Vol 4 (2) ◽  
pp. 01-05
Author(s):  
Mirzayeva Yu.T.
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Channel Blocker ◽  
Aortic Ring ◽  
Diterpenoid Alkaloids ◽  
Relaxant Effect ◽  
Ring Contraction ◽  
Voltage Dependent ◽  
Ca2 Channels ◽  
Isolated Rat

The aim of our research is to study the effect relaxant action of diterpenoid alkaloids talatisamine, 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine was studied using isolated rat aortic rings. Alkaloids significantly and dose-dependently inhibited contraction of the aortic rings caused by high KCl content. At the same time, under these conditions, alkaloids significantly reduced Ca2+-induced contraction of the aortic rings. The relaxing effects of alkaloids are significantly suppressed by verapamil, a potent potentiometer-dependent Ca2+ channel blocker. The alkaloids also significantly reduced norepinephrine-induced aortic ring contraction in normal as well as Ca2+ free Krebs solutions. The data obtained indicate that talatisamine, 14-benzoylthalatisamine and 14-O-acetylthalatisamine exhibit a pronounced relaxant effect in almost the same way in the case of contraction induced by a high content of KCl and norepinephrine. The mechanism of the relaxant action of alkaloids is probably complex and may include suppression of Ca2+influx through voltage-dependent and receptor-driven Ca2+ channels, as well as inhibition of Ca2+transport in the sarcoplasmic reticulum.

Properties of human atrial ICa at physiological temperatures and relevance to action potential

1997 ◽  
Vol 272 (1) ◽  
pp. H227-H235 ◽  
Author(s):  
G. R. Li ◽  
S. Nattel
Keyword(s):  
Action Potential ◽  
Human Atrium ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes ◽  
Maximum Current Density ◽  
Rate Dependent ◽  
Atrial Cells ◽  
Maximum Current ◽  
Reduced Rate

There are no published characterizations of Ca2+ current (ICa) at physiological temperatures in human atrium. Depolarization of human atrial myocytes at 36 degrees C elicited ICa that peaked at +10 mV, with a mean maximum current density of 10.8 +/- 1.1 pA/pF and no evidence for T-type current. Overlap between activation and inactivation curves and incomplete inactivation during pulses comparable to normal action potential duration (APD) were compatible with the observed role of ICa in maintaining the plateau. ICa was frequency dependent between 0.1 and 2 Hz and ICa blockade with 0.2 mM Cd2+ reduced rate-dependent changes in APD: under control, APD at 90% repolarization was 230 +/- 15 ms at 0.1 Hz and 178 +/- 14 ms at 2 Hz (decrease of 52 +/- 5 ms); with Cd2+, values were 121 +/- 7 ms at 0.1 H2 and 115 +/- 6 ms at 2 Hz (decrease of 6 +/- 3 ms, P < 0.01) Isoproterenol (1 microM) increased ICa and prolonged APD from 138 +/- 13 to 199 +/- 15 ms (P < 0.01). These results indicate that, in human atrial cells at 36 degrees C, the properties of L-type ICa contribute importantly to the rate-dependent and autonomic control of APD.

Voltage-clamp analysis of the ionic conductances in a leech neuron with a purely calcium-dependent action potential

1987 ◽  
Vol 58 (6) ◽  
pp. 1468-1484 ◽  
Author(s):  
J. Johansen ◽  
J. Yang ◽  
A. L. Kleinhaus
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Time Course ◽  
Outward Current ◽  
Time Constants ◽  
Exponential Time ◽  
Calcium Dependent ◽  
Voltage Dependent ◽  
Ca Currents ◽  
Single Exponential

1. The purely calcium-dependent action potential of the anterior lateral giant (ALG) cell in the leech Haementeria was examined under voltage clamp. 2. Analysis with ion substitutions showed that the ALG cell action potential is generated by only two time- and voltage-dependent conductance systems, an inward Ca-dependent current (ICa) and an outward Ca-dependent K current IK(Ca). 3. The kinetic properties of the inward current were examined both in Cs-loaded neurons with Ca as the current carrier as well as in Ba-containing Ringer solutions with Ba as the current carrier, since Ba effectively blocked all time- and voltage-dependent outward current. 4. During a maintained depolarization, Ba and Ca currents activated with a time constant tau m, they then inactivated with the decay following a single exponential time course with a time constant tau h. The time constants for decay of both Ba and Ca currents were comparable, suggesting that the mechanism of inactivation of ICa in the ALG cell is largely voltage dependent. In the range of potentials from 5 to 45 mV, tau m varied from 8 to 2 ms and tau h varied from 250 to 125 ms. 5. The activation of currents carried by Ba, after correction for inactivation, could be described reasonably well by the expression I'Ba = I'Ba(infinity) [1--exp(-t/tau m)]. 6. The steady-state activation of the Ba-conductance mBa(infinity) increased sigmoidally with voltage and was approximated by the equation mBa(infinity) = (1 + exp[(Vh-6)/3])-1. The steady-state inactivation hBa(infinity) varied with holding potential and could be described by the equation hBa(infinity) = [1 + exp(Vh + 10/7)]-1. Recovery from inactivation of IBa was best described by the sum of two exponential time courses with time constants of 300 ms and 1.75 s, respectively. 7. The outward current IK(Ca) developed very slowly (0.5–1 s to half-maximal amplitude) and did not inactivate during a 20-s depolarizing command pulse. Tail current decay of IK(Ca) followed a single exponential time course with voltage-dependent time constants of between 360 and 960 ms. The steady-state activation n infinity of IK(Ca) increased sigmoidally with depolarization as described by the equation n infinity = [1 + exp(Vh-13.5)/-8)]-1. 8. The reversal potentials of IK(Ca) tail currents were close to the expected equilibrium potential for potassium and they varied linearly with log [K]o with a slope of 51 mV. These results suggest a high selectivity of the conductance for K ions.(ABSTRACT TRUNCATED AT 400 WORDS)

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