Activation of P2Y receptors stimulates potassium and cation currents in acutely isolated human Müller (glial) cells
✍ Scribed by Andreas Bringmann; Thomas Pannicke; Michael Weick; Bernd Biedermann; Susann Uhlmann; Leon Kohen; Peter Wiedemann; Andreas Reichenbach
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 607 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0894-1491
No coin nor oath required. For personal study only.
✦ Synopsis
The ability of various neurotransmitters/neuroactive substances to induce fast, transient rises of Ca 2ϩ -activated K ϩ currents (I BK ) caused by release of Ca 2ϩ from intracellular stores was investigated in Mu ¨ller glial cells of the human retina. Mu ¨ller cells were enzymatically isolated from retinas of healthy donors or of patients with proliferative vitreoretinopathy, and the transmembrane ionic currents were recorded using the wholecell and the cell-attached patch-clamp techniques. The results of the screening experiments indicate that human Mu ¨ller cells express, in addition to GABA A and perhaps glutamatergic and cholinergic receptors, predominantly P2 receptors. ATP and other nucleotides exerted two effects on membrane currents: repetitive transient increases of the I BK amplitude and, in a subpopulation of cells investigated, the appearance of a transient cation conductance at negative potentials. ATP and UTP increased dose-dependently the I BK amplitude with half-maximal effects at 0.33 and 0.50 M, respectively. Since several different P2 receptor agonists increased the I BK , it is assumed that human Mu ¨ller cells express a mixture of different types of P2Y receptors. In cell-attached patches, extracellular application of ATP or UTP transiently increased the open probability of single putative BK channels. The increase of I BK and the appearance of the cation conductance in whole-cell records were abolished when intracellular Ca 2ϩ was buffered by a high-EGTA pipette solution or when IP 3 was included in the pipette solution. The expression of agonist-evoked transient cation currents was found to be stronger in cells from patients as compared to cells from healthy donors. It is concluded that human Mu ¨ller glial cells express P2Y receptors that, via IP 3 formation, cause intracellular Ca 2ϩ release. The increased intracellular Ca 2ϩ concentration stimulates the activity of BK channels and may induce opening of cation channels. Both the ATPinduced activity of BK channels and the increased expression of Ca 2ϩ -gated cation channels may be important in respect to proliferative Mu ¨ller cell gliosis. GLIA 37: 139-152, 2002.