Role of ion channels and subcellular Ca2+ signaling in arachidonic acid-induced dilation of pressurized retinal arterioles.
OBJECTIVE
To investigate the mechanisms responsible for the dilatation of rat retinal arterioles in response to arachidonic acid (AA).


METHODS
Changes in the diameter of isolated, pressurized rat retinal arterioles were measured in the presence of AA alone and following pre-incubation with pharmacologic agents inhibiting Ca(2+) sparks and oscillations and K(+) channels. Subcellular Ca(2+) signals were recorded in arteriolar myocytes using Fluo-4-based confocal imaging. The effects of AA on membrane currents of retinal arteriolar myocytes were studied using whole-cell perforated patch clamp recording.


RESULTS
Arachidonic acid dilated pressurized retinal arterioles under conditions of myogenic tone. Eicosatetraynoic acid (ETYA) exerted a similar effect, but unlike AA, its effects were rapidly reversible. Arachidonic acid-induced dilation was associated with an inhibition of subcellular Ca(2+) signals. Interventions known to block Ca(2+) sparks and oscillations in retinal arterioles caused dilatation and inhibited AA-induced vasodilator responses. Arachidonic acid accelerated the rate of inactivation of the A-type Kv current and the voltage dependence of inactivation was shifted to more negative membrane potentials. It also enhanced voltage-activated and spontaneous large-conductance calcium-activated K(+) (BK) currents, but only at positive membrane potentials. Pharmacologic inhibition of A-type Kv and BK currents failed to block AA-induced vasodilator responses. Arachidonic acid suppressed L-type Ca(2+) currents.


CONCLUSIONS
These results suggest that AA induces retinal arteriolar vasodilation by inhibiting subcellular Ca(2+)-signaling activity in retinal arteriolar myocytes, most likely through a mechanism involving the inhibition of L-type Ca(2+)-channel activity. Arachidonic acid actions on K(+) currents are inconsistent with a model in which K(+) channels contribute to the vasodilator effects of AA.
Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Northern Ireland, United Kingdom.
Joanna
J
Kur
Mary K
MK
McGahon
Jose A
JA
Fernández
C Norman
CN
Scholfield
J Graham
JG
McGeown
Tim M
TM
Curtis
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology / Q000502:physiology*; D001160:Arterioles / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004594:Electrophysiology; D023421:Models, Animal; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012161:Retinal Artery / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
D015221:Potassium Channels; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D002118:Calcium
arterioles; calcium signaling; ion channels