Arachidonic acid enhances amplitude and duration of myocyte
shortening and intracellular calcium transients in rat ventricular
myocytes.
Damron, Derek S., and Beth A. Summers.
Center for Anesthesiology Research, Division of Anesthesiology and
Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland,
Ohio 44195
APStracts 3:0311H, 1996.
Modulation of intracellular free calcium ([Ca2+]i) by inotropic
stimuli alters contractility in cardiac muscle. Arachidonic acid
(AA), a precursor for eicosanoid formation, is released in response
to receptor activation and myocardial ischemia and has been
demonstrated to alter K+ and Ca2+ channel activity. We investigated
the effects of AA on contractility by simultaneously measuring
[Ca2+]i and shortening in single, field-stimulated rat ventricular
myocytes. [Ca2+]i transients were measured using fura-2 and myocyte
shortening was assessed using video edge detection. AA stimulated a
doubling in the amplitude of the [Ca2+]i transient and a 2-fold
increase in myocyte shortening. In addition, AA stimulated a 30%
increase in the time to 50% diastolic [Ca2+]i and a 35% increase in
the time to 50% relengthening. These effects of AA were mediated by
AA itself (56?+/- 5%) and by cyclooxygenase metabolites. Pretreatment
with the protein kinase C inhibitors, staurosporine or chelerythrine,
nearly abolished (> 90% inhibition) these AA-induced effects.
Inhibition of voltage-gated K+ channels with 4-amino pyridine (4-AP)
mimicked the effects of AA. Addition of AA to the 4-AP treated
myocyte had no additional effect on parameters of contractile
function. These data indicate that AA alters the amplitude and
duration of Ca2+ transients and myocyte shortening via PKC-dependent
inhibition of voltage gated K+ channels. Release of AA by
phospholipases in response to receptor activation by endogenous
mediators or pathologic stimuli may be involved in mediating
inotropic responses in cardiac muscle.
Received 21 December 1995; accepted in final form 26 June 1996.
APS Manuscript Number H1191-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996