(-)-Isoproterenol modulation of maxi-K(+) channel in nonpigmented ciliary epithelial cells through a G-protein gated pathway.

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Bhattacharyya BJ, Lee E, Krupin D, Hockberger P, Krupin T

(-)-Isoproterenol modulation of maxi-K(+) channel in nonpigmented ciliary epithelial cells through a G-protein gated pathway.

Curr Eye Res. 2002 Mar;24(3):173-81.

PubMed ID

12221524 [ View in PubMed

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Abstract

PURPOSE: Adrenergic agents decrease intraocular pressure by reducing aqueous humor secretion from ciliary epithelial cells. Since the ionic concentration of aqueous humor contributes to intraocular pressure, we have investigated the effect of (-)-isoproterenol, a beta-adrenergic agonist on the maxi-K( +) channel in rabbit nonpigmented ciliary epithelial (NPE) cells. METHODS: Single-channel currents were recorded from the basolateral surface of acutely isolated NPE cells using patch clamp techniques. RESULTS: A calcium dependent maxi-K(+) channel was identified in 31% of cell-attached patches. In the excised condition the channel was activated in presence of calcium. In symmetrical K(+) solution a linear current-voltage relationship and unitary conductance of 158 +/- 15 pS was observed. Replacing K(+) with Na(+) the current-voltage curve shifted to the right and approached a reversal potential for K( +) ( approximately -80 mV). Barium (2 mM) from the intracellular side or iberiotoxin (50 nM) from the extracellular side blocked the channel activity. In cell-attached patches, the beta-receptor agonist (-)-isoproterenol (2.5 microM) increased channel open probability (P(o)) only when applied directly through the patch pipette. beta(2)-adrenoceptor antagonists (ICI-118, 551, l-timolol) blocked the channel activity more efficiently than the beta(1)-adrenoceptor antagonist betaxolol. In excised patches, (-)-isoproterenol increased baseline P(o) 5-fold (0.5 +/- 0.13) when GTP (100 microM) and GTPgammaS (100 microM) were present at the cytosolic surface of the pipette (control; P(o), 0.12 +/- 0.006). GTP augmented baseline channel activity (0.1 +/- 0.004) 7-fold (0.7 +/- 0.03) when (-)-isoproterenol was included in patch pipette. CONCLUSIONS: Rabbit NPE cells expressed maxi-K(+) channels on their basolateral surface. The adrenergic agonist (-)-isoproterenol activated these channels via a beta(2)-adrenoceptor that was modulated by a direct G-protein gated pathway.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Timolol	Beta-1 adrenergic receptor	Protein	Humans	Yes	Antagonist	Details