Real-time detection of mitochondrial inhibition at frog motor nerve terminals using increases in the spatial variance in probability of transmitter release.
The effects of Hg2+, methyl mercury, and flufenamic acid, all of which inhibit mitochondria, were examined at frog motor nerve terminals. Unbiased estimates of m (no. of transmitter quanta released), n (no. of functional release sites), p (probability of release), and vars p (spatial variance in p) were obtained using K(+)-induced asynchronous neurosecretion (m, n and p not having the same definitions as with nerve-evoked release). Transient but significant increases in m, n, p and vars p were found with all three agents. These findings indicate that mitochondrial inhibition and release of sequestered Ca2+ can be detected as a real-time increase in vars p. The results also suggest that changes in vars p might be used to differentiate between cellular (membrane) and subcellular (organellar) actions of drugs at the nerve terminal.
Provan
S D
SD
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614-0577, USA.
Miyamoto
M D
MD
D000818:Animals; D005439:Flufenamic Acid / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects*; D009046:Motor Neurons / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium; D011894:Rana pipiens; D013037:Spatial Behavior
D018377:Neurotransmitter Agents; D005439:Flufenamic Acid; D008628:Mercury; D011188:Potassium