Elevation of intracellular calcium reduces voltage-dependent potassium conductance in human T cells

Bregestovski, P.; Redkozubov, Alexei; Alexeev, A. V.

doi:10.1038/319776a0

Cited by 99 publications

(56 citation statements)

References 17 publications

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“…Dupuis et al (1989) have, in addition, found that in cells displaying a PHA-sensitive Ca2+ current, IK(V) was inhibited probably by an increase in internal Ca2+. Bregestovski, Redkozubov & Alexeev (1986) demonstrated that IK(V) is inhibited by intracellular Ca2+ and this relationship may account for the failure of other groups to detect any reproducible effect on IK(V) in human T-cells by PHA or phorbol esters (Deutsch, Krause & Lee, 1986;Schlichter, Sidell & Hagiwara, 1986b). Our patchclamp studies showed a low density of voltage-gated K+ channels in resting rat thymocytes and no activation of this class of K+ channels by ConA.…”

Section: Discussionmentioning

confidence: 78%

Ca(2+)‐activated K+ channels in rat thymic lymphocytes: activation by concanavalin A.

Mahaut‐Smith

Mason

1991

The Journal of Physiology

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SUMMARY1. The role of ion channels in the mitogenic response of rat thymic lymphocytes to concanavalin A (ConA) was studied using single-channel patch-clamp recordings and measurements of membrane potential with the fluorescent probe bis-oxonol.2. ConA (20 ,tg ml-') evoked a rapid membrane hyperpolarization; Indo-1 measurements indicated a concurrent increase in [Ca2+]i. The hyperpolarization was blocked by cytoplasmic loading with the Ca2+ buffer BAPTA (bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid), or charybdotoxin, a component of scorpion venom known to block K+ channels in lymphocytes.3. Cell-attached patch-clamp recordings showed that both ConA and the Ca2+ ionophore ionomycin activated channels with high selectivity for K+. Two conductance levels were observed -6-7 pS and 17-18 pS -measured as inward chord conductance at 60 mV from reversal potential (Erev) with 140 mM-KCl in the pipette.The current-voltage relationship for the larger channel displayed inward rectification and channel open probability was weakly dependent upon membrane potential. 4. These experiments provide the first direct evidence for mitogen-activated Ca2+-gated K+ channels (IK(Ca)) in lymphocytes. This conductance is relatively inactive in unstimulated rat thymocytes but following the intracellular Ca2+ rises induced by ConA, IK(ca) channels are activated and produce a significant hyperpolarization of the cell potential.

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Section: Discussionmentioning

confidence: 78%

Ca(2+)‐activated K+ channels in rat thymic lymphocytes: activation by concanavalin A.

Mahaut‐Smith

Mason

1991

The Journal of Physiology

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“…Current through voltage-gated K + channels can also be observed in many of the records as an upward deflection at more positive potentials. The ramp protocol with elevated [Ca2+]i reduces the size of voltage-gated currents, because the use-dependent inactivation exhibited by K(V) channels during repetitive depolarization is accentuated by calcium ions from the inside Bregestovski, Redkozubov, and Alexeev, 1986;Grissmer and Cahalan, 1989b).…”

Section: Activation Of K(ca) Channels During Whole-cell Recordingmentioning

confidence: 99%

Calcium-activated potassium channels in resting and activated human T lymphocytes. Expression levels, calcium dependence, ion selectivity, and pharmacology.

Grissmer

Nguyen

Cahalan

1993

The Journal of General Physiology

206

143

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Ca2+-activated K+[K(Ca)] channels in resting and activated human peripheral blood T lymphocytes were characterized using simultaneous patch-clamp recording and fura-2 monitoring of cytosolic Ca 2+ concentration, [Ca2+]i . Whole-cell experiments, using EGTA-buffered pipette solutions to raise [CaZ÷]i to 1 p,M, revealed a 25-fold increase in the number of conducting K(Ca) channels per cell, from an average of 20 in resting T cells to > 500 channels per cell in T cell blasts after mitogenic activation. The opening of K(Ca) channels in both whole-cell and inside-out patch experiments was highly sensitive to [Ca2+]i (Hill coefficient of 4, with a midpoint of ~ 300 nM). At optimal [Ca2+]i, the open probability of a K(Ca) channel was 0.3-0.5. K(Ca) channels showed little or no voltage dependence from -100 to 0 inV. Single-channel/-V curves were linear with a unitary conductance of 11 pS in normal Ringer and exhibited modest inward rectification with a unitary conductance of ~35 pS in symmetrical 160 mM K ÷. Permeability ratios, relative to K +, determined from reversal potential measurements were: K + (1.0) > Rb + (0.96) > NH~" (0.17) > Cs ÷ (0.07). Slope conductance ratios were: NH~ (1.2) > K + (1.0) > Rb + (0.6) > Cs ÷ (0.10). Extracellular Cs + or Ba 2+ each induced voltagedependent block of K(Ca) channels, with block increasing at hyperpolarizing potentials in a manner suggesting a site of block 75% across the membrane field from the outside. K(Ca) channels were blocked by tetraethylammonium (TEA) applied externally (Kd = 40 mM), but were unaffected by 10 mM TEA applied inside by pipette perfusion. K(Ca) channels were blocked by charybdotoxin (CTX) with a half-blocking dose of 3-4 nM, but were resistant to block by noxiustoxin (NTX) at 1-100 nM. Unlike K(Ca) channels in Jurkat T cells, the K(Ca) channels of normal resting or activated T cells were not blocked by apamin. We conclude that while K(Ca) and voltage-gated K + channels in the same cells share similarities in ion

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“…Experimental methods, data recording on FM tape (Bruel & Kjaer, Denmark) and offline computer (Labtam, Australia) analysis procedures are similar to those previously described elsewhere in detail (Bregestovski et al, 1986;Takeda et al, 1987). Pipettes for whole cell recording had resistances of 3-7 MO.…”

Section: Electrophysiologymentioning

confidence: 99%

Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein

Bregestovski

Bakhramov

Danilov

et al. 1988

British J Pharmacology

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1 The membrane response to applied histamine of cultured endothelial cells from human umbilical vein was studied by use of whole cell and single channel patch clamp techniques. A value of -27 + 1.4 mV was found for the resting potential under whole cell current clamp. No voltage-gated currents were seen at either the macroscopic or single channel levels. 2 At holding potentials of -20 to -40 mV, histamine evoked slow rising, long lasting whole cell inward currents. The inward current was associated with depolarization and decreased input resistance. The calcium ionophore A23187 provoked similar whole cell inward currents. 3 Single channel currents were observed in cell-attached and inside-out patches for both histamine and A23187. The single channel conductance was about 20 pS with a mean open time of 5 ms and a reversal potential of OmV in symmetrical potassium solutions. Internal sodium blocked outward going currents. 4 For cell-attached patches, histamine-dependent channel activity required external calcium and was also seen when histamine was present in the bath but not the pipette. Recording from insideout patches revealed that decreases in 'internal' calcium resulted in the disappearance of channel activity. 5 The histamine-dependent inward current appears to involve calcium-dependent activation of cationic channels.

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Elevation of intracellular calcium reduces voltage-dependent potassium conductance in human T cells

Cited by 99 publications

References 17 publications

Ca(2+)‐activated K+ channels in rat thymic lymphocytes: activation by concanavalin A.

Ca(2+)‐activated K+ channels in rat thymic lymphocytes: activation by concanavalin A.

Calcium-activated potassium channels in resting and activated human T lymphocytes. Expression levels, calcium dependence, ion selectivity, and pharmacology.

Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein

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