Effects of arachidonic acid on unitary calcium currents in rat sympathetic neurons.
We have characterized the actions of arachidonic acid (AA) on whole cell and unitary calcium (Ca2+) currents in rat neonatal superior cervical ganglion (SCG) neurons using barium (Ba2+) as the charge carrier. Whole cell currents were elicited by stepping the membrane potential from -90 mV to +10 mV. Arachidonic acid (5 microM) was introduced into the bath in the continued presence of 1 microM (+)-202-791, an L-type Ca2+ channel agonist. Under these conditions, the peak current, comprised mainly of N-type current, and a slow, (+)-202-791-induced component of the tail current were inhibited by 67 +/- 6 and 60 +/- 10 %, respectively, indicating that AA inhibits both N- and L-type currents. At a test potential of +30 mV, AA (5 microM) decreased unitary L- and N-type Ca2+ channel open probability (Po) in cell-attached patches that contained a single channel. For both channels, the underlying causes of the decrease in Po were similar. Arachidonic acid caused an increase in the percentage of null sweeps and in the number of null sweeps that clustered together. In sweeps with activity, the average number of openings per sweep decreased, while first latency and mean closed time increased. Arachidonic acid had no significant effect on unitary current amplitude or mean open time. Our findings are the first description of the inhibition of unitary L- and N-type Ca2+ channel activity by AA and are consistent with both channels spending more time in their null mode and with increased dwell time in one or more closed states.
Liu
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Department of Physiology and Program in Neuroscience, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA.
Rittenhouse
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AR
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000494:pharmacology*; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D001464:Barium; D016718:Arachidonic Acid; D002118:Calcium