Calcium activates SK channels in the intact human lens.

Abstract

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.

• Authors: Jeremy D Rhodes, David J Collison, George Duncan
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 44 Issue 9 Pg. 3927-32 (Sep 2003) ISSN: 0146-0404 [Print] United States
• PMID: 12939311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Agonists
• Potassium Channels
• Potassium Channels, Calcium-Activated
• Small-Conductance Calcium-Activated Potassium Channels
• Trifluoperazine
• Apamin
• Ionomycin
• Protein-Tyrosine Kinases
• GTP-Binding Proteins
• Calcium
• Fura-2

Topics

• Aged
• Aged, 80 and over
• Apamin (pharmacology)
• Calcium (physiology)
• Calcium Channel Agonists (pharmacology)
• Calcium Signaling (physiology)
• Electrophysiology
• Fura-2
• GTP-Binding Proteins (agonists, metabolism)
• Humans
• Ionomycin (pharmacology)
• Lens, Crystalline (drug effects, metabolism)
• Membrane Potentials (drug effects)
• Middle Aged
• Polymerase Chain Reaction
• Potassium Channels (genetics, metabolism)
• Potassium Channels, Calcium-Activated
• Protein-Tyrosine Kinases (metabolism)
• Small-Conductance Calcium-Activated Potassium Channels
• Trifluoperazine (pharmacology)