Acute actions of marine toxin latrunculin A on the electrophysiological properties of cultured dorsal root ganglion neurones.
The effects of latrunculin A, isolated from the nudibranch Chromodoris sp., on the excitability of neonatal rat cultured dorsal root ganglion neurones were investigated using patch-clamp recording and Ca(2+) imaging techniques. Under current-clamp conditions, acute application of latrunculin A (100 microM) reversibly induced multiple action potential firing and significantly increased action potential duration. No significant effects on action potential peak amplitude, threshold of action potential firing, resting membrane potential and input resistance were observed. Under voltage-clamp conditions, significant and dose-dependent suppression of K(+) current was seen with 10-100 microM latrunculin A. Additionally, a significant difference between inhibition of the current measured at the peak and the end of a 100 ms voltage step was seen with 100 microM latrunculin A. Fura-2 fluorescence Ca(2+) imaging revealed that latrunculin A (100 microM) significantly inhibited Ca(2+) transients evoked by KCl-induced depolarisation in all neurones. In 36% of DRG neurones, latrunculin A alone had no effect on intracellular Ca(2+). In 64% of neurones, latrunculin A alone evoked a transient rise in intracellular Ca(2+). Moreover, latrunculin A (10-100 microM) significantly inhibited the mean high voltage-activated Ca(2+) current. The effects of latrunculin A on action potential firing and K(+) currents were attenuated by intracellular phalloidin, an indication that these effects are mediated through actin disruption.
Houssen
Wael E
WE
Marine Natural Products Laboratory, Chemistry Department, University of Aberdeen, Scotland, UK. w.houssen@abdn.ac.uk
Jaspars
Marcel
M
Wease
Kerrie N
KN
Scott
Roderick H
RH
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005071:Evoked Potentials / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010590:Phalloidine / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D051381:Rats; D013844:Thiazoles / Q000037:antagonists & inhibitors / Q000633:toxicity*; D053778:Thiazolidines
D019086:Bridged Bicyclo Compounds, Heterocyclic; D015220:Calcium Channels; D013844:Thiazoles; D053778:Thiazolidines; D010590:Phalloidine; D011188:Potassium; C037067:latrunculin A