scholarly journals Biphasic voltage-dependent inactivation of human NaV1.3, 1.6 and 1.7 Na+channels expressed in rodent insulin-secreting cells

2018 ◽  
Vol 596 (9) ◽  
pp. 1601-1626 ◽  
Author(s):  
Mahdieh Godazgar ◽  
Quan Zhang ◽  
Margarita V. Chibalina ◽  
Patrik Rorsman
Keyword(s):  
Na Channels ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Insulin Secreting Cells

scholarly journals Single Ion Occupancy and Steady-state Gating of Na Channels in Squid Giant Axon

2002 ◽  
Vol 119 (3) ◽  
pp. 235-250 ◽  
Author(s):  
Robert F. Rakowski ◽  
David C. Gadsby ◽  
Paul De Weer
Keyword(s):  
Steady State ◽  
Flux Ratio ◽  
Giant Axon ◽  
Boltzmann Distribution ◽  
Na Channels ◽  
Open Probability ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Effective Valence ◽  
Equilibrium Dissociation

The properties of the small fraction of tetrodotoxin (TTX)-sensitive Na channels that remain open in the steady state were studied in internally dialyzed voltage clamped squid giant axons. The observed Ussing flux ratio exponent (n′) of 0.97 ± 0.03 (calculated from simultaneous measurements of TTX-sensitive current and 22Na efflux) and nonindependent behavior of Na current at high internal [Na] are explained by a one-site (“1s”) permeation model characterized by a single effective binding site within the channel pore in equilibrium with internal Na ions (apparent equilibrium dissociation constant KNai(0) = 0.61 ± 0.08 M). Steady-state open probability of the TTX-sensitive channels can be modeled by the product pap∞, where pa represents voltage-dependent activation described by a Boltzmann distribution with midpoint Va = −7 mV and effective valence za = 3.2 (Vandenberg, C.A., and F. Bezanilla. 1991. Biophys. J. 60:1499–1510) coupled to voltage-independent inactivation by an equilibrium constant (Bezanilla, F., and C.M. Armstrong. 1977. J. Gen. Physiol. 70:549–566) Keq = 770. The factor p∞ represents voltage-dependent inactivation with empirical midpoint V∞= −83 ± 5 mV and effective valence z∞ = 0.55 ± 0.03. The composite pap∞1s model describes the steady-state voltage dependence of the persistent TTX-sensitive current well.

scholarly journals Activation-inactivation of potassium channels and development of the potassium-channel spike in internally perfused squid giant axons.

1981 ◽  
Vol 78 (1) ◽  
pp. 43-61 ◽  
Author(s):  
I Inoue
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Voltage Clamp ◽  
Time Constant ◽  
Equilibrium Potential ◽  
Giant Axons ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Time Courses ◽  
Calcium Permeability

A spike that is the result of calcium permeability through potassium channels was separated from the action potential is squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution by blocking sodium channels with tetrodotoxin. Currents through potassium channels were studied under voltage clamp. The records showed a clear voltage-dependent inactivation of the currents. The inactivation was composed of at least two components; one relatively fast, having a time constant of 20--30 ms, and the other very slow, having a time constant of 5--10 s. Voltage clamp was carried out with a variety of salt compositions in both the internal and external solutions. A similar voltage-dependent inactivation, also composed of the two components, was recognized in all the current through potassium channels. Although the direction and intensity of current strongly depended on the salt composition of the solutions, the time-courses of these currents at corresponding voltages were very similar. These results strongly suggest that the inactivation of the currents in attributable to an essential, dynamic property of potassium channels themselves. Thus, the generation of a potassium-channel spike can be understood as an event that occurs when the equilibrium potential across the potassium channel becomes positive.

Halothane Inhibition of Recombinant Cardiac L-type Ca2+ Channels Expressed in HEK-293 Cells

2005 ◽  
Vol 103 (6) ◽  
pp. 1156-1166 ◽  
Author(s):  
Kevin J. Gingrich ◽  
Son Tran ◽  
Igor M. Nikonorov ◽  
Thomas J. Blanck
Keyword(s):  
Charge Transfer ◽  
Calcium Channels ◽  
Dependent Manner ◽  
Current Time ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Dependent Inactivation ◽  
Voltage Dependent

Background Volatile anesthetics depress cardiac contractility, which involves inhibition of cardiac L-type calcium channels. To explore the role of voltage-dependent inactivation, the authors analyzed halothane effects on recombinant cardiac L-type calcium channels (alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1), which differ by the alpha2/delta1 subunit and consequently voltage-dependent inactivation. Methods HEK-293 cells were transiently cotransfected with complementary DNAs encoding alpha1C tagged with green fluorescent protein and beta2a, with and without alpha2/delta1. Halothane effects on macroscopic barium currents were recorded using patch clamp methodology from cells expressing alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1 as identified by fluorescence microscopy. Results Halothane inhibited peak current (I(peak)) and enhanced apparent inactivation (reported by end pulse current amplitude of 300-ms depolarizations [I300]) in a concentration-dependent manner in both channel types. alpha2/delta1 coexpression shifted relations leftward as reported by the 50% inhibitory concentration of I(peak) and I300/I(peak)for alpha1Cbeta2a (1.8 and 14.5 mm, respectively) and alpha1Cbeta2aalpha2/delta1 (0.74 and 1.36 mm, respectively). Halothane reduced transmembrane charge transfer primarily through I(peak) depression and not by enhancement of macroscopic inactivation for both channels. Conclusions The results indicate that phenotypic features arising from alpha2/delta1 coexpression play a key role in halothane inhibition of cardiac L-type calcium channels. These features included marked effects on I(peak) inhibition, which is the principal determinant of charge transfer reductions. I(peak) depression arises primarily from transitions to nonactivatable states at resting membrane potentials. The findings point to the importance of halothane interactions with states present at resting membrane potential and discount the role of inactivation apparent in current time courses in determining transmembrane charge transfer.

Altered frequency-dependent inactivation and steady-state inactivation of polyglutamine-expanded α1A in SCA6

2007 ◽  
Vol 292 (3) ◽  
pp. C1078-C1086 ◽  
Author(s):  
Haiyan Chen ◽  
Erika S. Piedras-Rentería
Keyword(s):  
Steady State ◽  
Late Onset ◽  
Spinocerebellar Ataxia Type ◽  
Gain Of Function ◽  
Calcium Dependent ◽  
Spinocerebellar Ataxia Type 6 ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
Activity Dependent

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease of the cerebellum and inferior olives characterized by a late-onset cerebellar ataxia and selective loss of Purkinje neurons ( 15 , 16 ). SCA6 arises from an expansion of the polyglutamine tract located in exon 47 of the α1A (P/Q-type calcium channel) gene from a nonpathogenic size of 4 to 18 glutamines (CAG4–18) to CAG19–33 in SCA6. The molecular basis of SCA6 is poorly understood. To date, the biophysical properties studied in heterologous systems support both a gain and a loss of channel function in SCA6. We studied the behavior of the human α1A isoform, previously found to elicit a gain of function in disease ( 41 ), focusing on properties in which the COOH terminus of the channel is critical for function: we analyzed the current properties in the presence of β4- and β2a-subunits (both known to interact with the α1A COOH terminus), current kinetics of activation and inactivation, calcium-dependent inactivation and facilitation, voltage-dependent inactivation, frequency dependence, and steady-state activation and inactivation properties. We found that SCA6 channels have decreased activity-dependent inactivation and a depolarizing shift (+6 mV) in steady-state inactivation properties consistent with a gain of function.

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

scholarly journals CaBP1 Regulates Voltage-dependent Inactivation and Activation of CaV1.2 (L-type) Calcium Channels

2011 ◽  
Vol 286 (16) ◽  
pp. 13945-13953 ◽  
Author(s):  
Shimrit Oz ◽  
Vladimir Tsemakhovich ◽  
Carl J. Christel ◽  
Amy Lee ◽  
Nathan Dascal
Keyword(s):  
Calcium Channels ◽  
Dependent Inactivation ◽  
Voltage Dependent

Regulation of Rho/ROCK signaling in airway smooth muscle by membrane potential and [Ca2+]i

2005 ◽  
Vol 289 (4) ◽  
pp. L574-L582 ◽  
Author(s):  
Caiqiong Liu ◽  
Jianmin Zuo ◽  
Evi Pertens ◽  
Peter B. Helli ◽  
Luke J. Janssen
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Signal Transduction Pathway ◽  
Cyclopiazonic Acid ◽  
Membrane Depolarization ◽  
Rock Inhibitor ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
G Protein Coupled ◽  
Evoked Contractions

Recently, we have shown that Rho and Rho-activated kinase (ROCK) may become activated by high-millimolar KCl, which had previously been widely assumed to act solely through opening of voltage-dependent Ca2+ channels. In this study, we explored in more detail the relationship between membrane depolarization, Ca2+ currents, and activation of Rho/ROCK in bovine tracheal smooth muscle. Ca2+ currents began to activate at membrane voltages more positive than −40 mV and were maximally activated above 0 mV; at the same time, these underwent time- and voltage-dependent inactivation. Depolarizing intact tissues by KCl challenge evoked contractions that were blocked equally, and in a nonadditive fashion, by nifedipine or by the ROCK inhibitor Y-27632. Other agents that elevate intracellular calcium concentration ([Ca2+]i) by pathways independent of G protein-coupled receptors, namely the SERCA-pump inhibitor cyclopiazonic acid and the Ca2+ ionophore A-23187, evoked contractions that were also largely reduced by Y-27632. KCl directly increased Rho and ROCK activities in a concentration-dependent fashion that paralleled closely the effect of KCl on tone and [Ca2+]i, as well as the voltage-dependent Ca2+ currents that were measured over the voltage ranges that are evoked by 0–120 mM KCl. Through the use of various pharmacological inhibitors, we ruled out roles for Ca2+/calmodulin-dependent CaM kinase II, protein kinase C, and protein kinase A in mediating the KCl-stimulated changes in tone and Rho/ROCK activities. In conclusion, Rho is activated by elevation of [Ca2+]i (although the signal transduction pathway underlying this Ca2+ dependence is still unclear) and possibly also by membrane depolarization per se.

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