Activation process of calcium-dependent potassium channel in euhadra neurons: Involvement of calcium/calmodulin and subsequent protein phosphorylation

The human intermediate conductance calcium-activated potassium channel, KCa3.1, is involved in several pathophysiological conditions playing a critical role in cell secretory machinery and calcium signalling. The recent cryo-EM analysis provides new insights for understanding the modulation by both endogenous and pharmacological agents. A typical feature of this channel is the low open probability in saturating calcium concentrations and its modulation by potassium channel openers (KCOs), such as benzo imidazolone 1-EBIO, without changing calcium-dependent activation. In this paper, we proposed a model of KCOs action in the modulation of channel activity. The KCa3.1 channel has a very rich pharmacological profile with several classes of molecules that selectively interact with different binding sites of the channel. Among them, benzo imidazolones can be openers (positive modulators such as 1-EBIO, DC-EBIO) or blockers (negative modulators such as NS1619). Through computation modelling techniques, we identified the 1,4-benzothiazin-3-one as a promising scaffold to develop new KCa3.1 channel modulators. Further studies are needed to explore the potential use of 1-4 benzothiazine- 3-one in KCa3.1 modulation and its pharmacological application.

Download Full-text

Thyrotropin-releasing hormone rapidly and transiently stimulates cytosolic calcium-dependent protein phosphorylation in GH3 pituitary cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)34417-x ◽

1982 ◽

Vol 257 (13) ◽

pp. 7566-7573 ◽

Cited By ~ 15

Author(s):

D S Drust ◽

T F Martin

Keyword(s):

Protein Phosphorylation ◽

Cytosolic Calcium ◽

Thyrotropin Releasing Hormone ◽

Pituitary Cells ◽

Releasing Hormone ◽

Calcium Dependent ◽

Dependent Protein

Download Full-text

Calcium-Dependent Protein Phosphorylation in Germinated Pollen

Molecular and Cellular Aspects of Calcium in Plant Development ◽

10.1007/978-1-4613-2177-4_53 ◽

1986 ◽

pp. 345-346

Author(s):

Gideon M. Polya ◽

Vito Micucci ◽

Anne L. Rae ◽

Philip J. Harris ◽

Adrienne E. Clarke

Keyword(s):

Protein Phosphorylation ◽

Calcium Dependent ◽

Dependent Protein ◽

Germinated Pollen

Download Full-text

Action Potentials in Rhodnius Oocytes: Repolarization is Sensitive to Potassium Channel Blockers

Journal of Experimental Biology ◽

10.1242/jeb.126.1.119 ◽

1986 ◽

Vol 126 (1) ◽

pp. 119-132

Author(s):

M. J. O'DONNELL

Keyword(s):

Potassium Channel ◽

Action Potentials ◽

Potassium Conductance ◽

Channel Blockers ◽

Calcium Dependent ◽

Outward Rectification ◽

Current Voltage ◽

Potassium Channel Blockers ◽

Potassium Conductances ◽

Voltage Dependent

Depolarization of Rhodnius oocytes evokes action potentials (APs) whose rising phase is calcium-dependent. The ionic basis for the repolarizing (i.e. falling) phase of the AP was examined. Addition of potassium channel blockers (tetraethylammonium, tetrabutylammonium, 4-aminopyridine, atropine) to the bathing saline increased the duration and overshoot of APs. Intracellular injection of tetraethyl ammonium had similar effects. These results suggest that a voltage-dependent potassium conductance normally contributes to repolarization. Repolarization does not require a chloride influx, because substitution of impermeant anions for chloride did not increase AP duration. AP duration and overshoot actually decreased progressively when chloride levels were reduced. Current/voltage curves show inward and outward rectification, properties often associated with potassium conductances. Outward rectification was largely blocked by external tetraethylammonium. Possible functions of the rectifying properties of the oocyte membrane are discussed.

Download Full-text