Collison, DJ

Duncan, G

Rhodes, JD

English

Purpose: Apamin-sensitive, calcium-activated SK potassium channels have been implicated in schizophrenia and myotonic dystrophy (MD), and both conditions carry an increased risk of cataract. The presence and functional activity of SK channels were therefore investigated in the human lens. Methods: The expression of all three members of the SK channel family was quantified by PCR. Their functional activity was investigated by using electrophysiological and calcium-imaging techniques. Lens voltage was monitored by inserting a single electrode into the intact human lens, and changes in intracellular calcium were recorded simultaneously after fura-2 incorporation. Results: Expression of all three SK family members was detected in both anterior and equatorial lens epithelial cells. Application of either G-protein (e.g., adenosine triphosphate [ATP]) or tyrosine kinase (EGF) receptor agonists induced a hyperpolarization of lens voltage that was accompanied by an increase in intracellular calcium. The calcium ionophore ionomycin also induced a rapid hyperpolarization. The hyperpolarizing responses were abolished by apamin and trifluoperazine and were accentuated by the SK channel activator 1-ethyl-2-benzimidazolinone (1-EBIO). Conclusions: SK channels are an integral part of the G-protein and tyrosine kinase calcium signaling mechanisms in the human lens, and their activation is inhibited by certain anti-psychotic drugs. These findings help explain why a change in channel activity, whether by abnormal gene expression or by drug intervention, can lead to cataract

Rhodes, Jeremy D.

Collison, David J.

Duncan, George

University of East Anglia digital repository

A study of human lens cell growth in vitro: a model for posterior capsule opacification. Invest Ophthalmol Vis Sci.

Acetylcholine modulation of the short-circuit current across the rabbit lens. Exp Eye Res.

Acetylcholine-induced electrical responses in intact human, rat and rabbit lenses. Exp Eye Res.

An association of CAG repeats at the KCNN3 locus with symptom dimensions of schizophrenia. Biol Psychiatry.

CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia. Biol Psychiatry.

Calcium cell signalling and cataract. Prog Retinal Eye Res.

Calcium-activated potassium channels. Curr Opin Neurobiol.

Calmodulin antagonists induce changes in lens permeability and transparency. Curr Eye Res.

Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1.

Chlorpromazine effects upon rabbit lens water and electrolyte balance. Exp Eye Res.

Decreased membrane-permeability to potassium is responsible for the cell-volume increase that drives lens fibre cell elongation.

Diseases of the lens and vitreous. In:

Experimental chlorpromazine cataracts. Invest Ophthalmol Vis Sci.

Exposure to phenothiazine drugs and risk of cataract. Arch Ophthalmol.

Expression of apamin receptors in muscle of patients with myotonic muscular dystrophy.

Human lens membrane cation permeability increases with age. Invest Ophthalmol Vis Sci.

Ion analysis of human cataractous lenses. Exp Eye Res.

Ion transporters and receptors in cDNA libraries from lens and cornea epithelia. Curr Eye Res.

Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder. Mol Psychiatry.

Lens epithelial changes and mutated gene expression in patients with myotonic dystrophy.

Lenticular opacities induced in mice by chlorpromazine. Arch Ophthalmol.

Mechanism of calcium gating in small-conductance calcium-activated potassium channels.

Molecular characterization of volume-sensitive SKCa channels in human liver cell lines.

Nuclear localization and dominant-negative suppression by a mutant SKCa3 N-terminal channel fragment identified in a patient with schizophrenia.

Ocular changes in dystrophia myotonica.

Pharmacological characterization of the human small conductance calcium-activated potassium channel hSK3 reveals sensitivity to tricyclic antidepressants and antipsychotic phenothiazines.

Pharmacological modulation of SK3 channels.

Possible role of apamin-sensitive K channels in myotonic dystrophy. Muscle Nerve.

Quantitative expression analysis of the small conductance calcium-activated potassium channels, SK1, SK2 and SK3, in human brain. Mol Brain Res.

Regional differences in functional receptor distribution and calcium mobilization in the intact lens. Invest Ophthalmol Vis Sci.

Regulation of cloned, Ca2-activated K channels by cell volume changes. Pflugers Arch.

Small-conductance, calcium-activated potassium channels from mammalian brain.

The effect of 2–4 dinitrophenol on cell to cell communication in the frog lens. Exp Eye Res.

The human lens possesses acetylcholine receptors that are functional throughout life. Exp Eye Res.

Calcium activates SK channels in the intact human lens.

Abstract

Similar works

Full text

Available Versions

University of East Anglia digital repository

Crossref