Voltage-dependent K+-channel responses during activation and damage in alveolar macrophages induced by quartz particles

Voltage-gated K+ channels are key regulators of neuronal excitability. The Kv2.1 voltage-gated K+ channel is the major delayed rectifier K+ channel expressed in most central neurons, where it exists as a highly phosphorylated protein. Kv2.1 plays a critical role in homoeostatic regulation of intrinsic neuronal excitability through its activity- and calcineurin-dependent dephosphorylation. Here, we review studies leading to the identification and functional characterization of in vivo Kv2.1 phosphorylation sites, a subset of which contribute to graded modulation of voltage-dependent gating. These findings show that distinct developmental-, cell- and state-specific regulation of phosphorylation at specific sites confers a diversity of functions on Kv2.1 that is critical to its role as a regulator of intrinsic neuronal excitability.

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Ba2+, TEA+, and quinine effects on apical membrane K+ conductance and maxi K+ channels in gallbladder epithelium

AJP Cell Physiology ◽

10.1152/ajpcell.1990.259.1.c56 ◽

1990 ◽

Vol 259 (1) ◽

pp. C56-C68 ◽

Cited By ~ 23

Author(s):

Y. Segal ◽

L. Reuss

Keyword(s):

Apical Membrane ◽

Membrane Conductance ◽

Membrane Resistance ◽

K Channel ◽

Dependent Manner ◽

Gallbladder Epithelium ◽

Concentration Dependent Manner ◽

K Channels ◽

Voltage Dependent ◽

Channel Currents

The apical membrane of Necturus gallbladder epithelium contains a voltage-activated K+ conductance [Ga(V)]. Large-conductance (maxi) K+ channels underlie Ga(V) and account for 17% of the membrane conductance (Ga) under control conditions. We examined the Ba2+, tetraethylammonium (TEA+), and quinine sensitivities of Ga and single maxi K+ channels. Mucosal Ba2+ addition decreased resting Ga in a concentration-dependent manner (65% block at 5 mM) and decreased Ga(V) in a concentration- and voltage-dependent manner. Mucosal TEA+ addition also decreased control Ga (60% reduction at 5 mM). TEA+ block of Ga(V) was more potent and less voltage dependent that Ba2+ block. Maxi K+ channels were blocked by external Ba2+ at millimolar levels and by external TEA+ at submillimolar levels. At 0.3 mM, quinine (mucosal addition) hyperpolarized the cell membranes by 6 mV and reduced the fractional apical membrane resistance by 50%, suggesting activation of an apical membrane K+ conductance. At 1 mM, quinine both activated and blocked K(+)-conductive pathways. Quinine blocked maxi K+ channel currents at submillimolar concentrations. We conclude that 1) Ba2+ and TEA+ block maxi K+ channels and other K+ channels underlying resting Ga; 2) parallels between the Ba2+ and TEA+ sensitivities of Ga(V) and maxi K+ channels support a role for these channels in Ga(V); and 3) quinine has multiple effects on K(+)-conductive pathways in gallbladder epithelium, which are only partially explained by block of apical membrane maxi K+ channels.

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K+ channel blockade in the NTS alters efficacy of two cardiorespiratory reflexes in vivo

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.3.r677 ◽

1998 ◽

Vol 274 (3) ◽

pp. R677-R685 ◽

Cited By ~ 2

Author(s):

James W. Butcher ◽

Julian F. R. Paton

Keyword(s):

Potassium Channel ◽

Neuronal Excitability ◽

Baroreceptor Reflex ◽

Right Atrial ◽

K Channel ◽

Reflex Bradycardia ◽

Potassium Conductances ◽

Voltage Dependent

We investigated the role of potassium conductances in the nucleus of the solitary tract (NTS) in determining the efficacy of the baroreceptor and cardiopulmonary reflexes in anesthetized rats. The baroreceptor reflex was elicited with an intravenous injection of phenylephrine to evoke a reflex bradycardia, and the cardiopulmonary reflex was evoked with a right atrial injection of phenylbiguanide. Microinjection of two Ca-dependent potassium channel antagonists (apamin and charybdotoxin) into the NTS potentiated the baroreceptor reflex bradycardia. This may reflect the increased neuronal excitability observed previously in vitro with these blockers. In contrast, the Ca-dependent potassium channel antagonists attenuated the cardiopulmonary reflex, whereas voltage-dependent potassium channel antagonists (4-aminopyridine and dendrotoxin) attenuated both the baro- and cardiopulmonary reflexes when microinjected into the NTS. The possibility that the reflex attenuation observed indicates a predominant distribution of certain potassium channels on γ-aminobutyric acid interneurons is discussed.

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Complexity of the outward K+ current of the rat megakaryocyte

AJP Cell Physiology ◽

10.1152/ajpcell.1997.272.5.c1525 ◽

1997 ◽

Vol 272 (5) ◽

pp. C1525-C1531 ◽

Cited By ~ 5

Author(s):

E. Romero ◽

R. Sullivan

Keyword(s):

K Channel ◽

Delayed Rectifier ◽

Channel Blockers ◽

Excitable Cells ◽

Electrophysiological Properties ◽

Relative Contribution ◽

Delayed Rectifier Current ◽

Dependent Inactivation ◽

Voltage Dependent ◽

K Current

Megakaryocytes isolated from rat bone marrow express a voltage-dependent, outward K+ current with complex kinetics of activation and inactivation. We found that this current could be separated into at least two components based on differential responses to K+ channel blockers. One component, which exhibited features of the "transient" or "A-type" K+ current of excitable cells, was more strongly blocked by 4-aminopyridine (4-AP) than by tetrabutylammonium (TBA). This current, which we designated as "4-AP-sensitive" current, activated rapidly at potentials more positive than -40 mV and subsequently underwent rapid voltage-dependent inactivation. A separate current that activated slowly was blocked much more effectively by TBA than by 4-AP. This "TBA-sensitive" component, which resembled a typical delayed rectifier current, was much more resistant to voltage-dependent inactivation. The relative contribution of each of these components varied from cell to cell. The effect of charybdotoxin was similar to that of 4-AP. Our data indicate that the voltage-dependent K+ current of resting megakaryocytes is more complex than heretofore believed and support the emerging concept that megakaryocytes possess intricate electrophysiological properties.

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Potassium channel types in arterial chemoreceptor cells and their selective modulation by oxygen.

The Journal of General Physiology ◽

10.1085/jgp.100.3.401 ◽

1992 ◽

Vol 100 (3) ◽

pp. 401-426 ◽

Cited By ~ 83

Author(s):

M D Ganfornina ◽

J López-Barneo

Keyword(s):

Time Course ◽

Single Channel ◽

K Channel ◽

Open Probability ◽

K Channels ◽

Glomus Cells ◽

Control Value ◽

Voltage Dependent ◽

K Current ◽

Chemoreceptor Cells

Single K+ channel currents were recorded in excised membrane patches from dispersed chemoreceptor cells of the rabbit carotid body under conditions that abolish current flow through Na+ and Ca2+ channels. We have found three classes of voltage-gated K+ channels that differ in their single-channel conductance (gamma), dependence on internal Ca2+ (Ca2+i), and sensitivity to changes in O2 tension (PO2). Ca(2+)-activated K+ channels (KCa channels) with gamma approximately 210 pS in symmetrical K+ solutions were observed when [Ca2+]i was greater than 0.1 microM. Small conductance channels with gamma = 16 pS were not affected by [Ca2+]i and they exhibited slow activation and inactivation time courses. In these two channel types open probability (P(open)) was unaffected when exposed to normoxic (PO2 = 140 mmHg) or hypoxic (PO2 approximately 5-10 mmHg) external solutions. A third channel type (referred to as KO2 channel), having an intermediate gamma(approximately 40 pS), was the most frequently recorded. KO2 channels are steeply voltage dependent and not affected by [Ca2+]i, they inactivate almost completely in less than 500 ms, and their P(open) reversibly decreases upon exposure to low PO2. The effect of low PO2 is voltage dependent, being more pronounced at moderately depolarized voltages. At 0 mV, for example, P(open) diminishes to approximately 40% of the control value. The time course of ensemble current averages of KO2 channels is remarkably similar to that of the O2-sensitive K+ current. In addition, ensemble average and macroscopic K+ currents are affected similarly by low PO2. These observations strongly suggest that KO2 channels are the main contributors to the macroscopic K+ current of glomus cells. The reversible inhibition of KO2 channel activity by low PO2 does not desensitize and is not related to the presence of F-, ATP, and GTP-gamma-S at the internal face of the membrane. These results indicate that KO2 channels confer upon glomus cells their unique chemoreceptor properties and that the O2-K+ channel interaction occurs either directly or through an O2 sensor intrinsic to the plasma membrane closely associated with the channel molecule.

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