A pyridinium derivative from Red Sea soft corals inhibited voltage-activated potassium conductances and increased excitability of rat cultured sensory neurones.
BACKGROUND
Whole cell patch clamp recording and intracellular Ca2+ imaging were carried out on rat cultured dorsal root ganglion (DRG) neurones to characterize the actions of crude extracts and purified samples from Red Sea soft corals. The aim of the project was to identify compounds that would alter the excitability of DRG neurones.


RESULTS
Crude extracts of Sarcophyton glaucum and Lobophyton crassum attenuated spike frequency adaptation causing DRG neurones to switch from firing single action potentials to multiple firing. The increase in excitability was associated with enhanced KCl-evoked Ca2+ influx. The mechanism of action of the natural products in the samples from the soft corals involved inhibition of voltage-activated K+ currents. An active component of the crude marine samples was identified as 3-carboxy-1-methyl pyridinium (trigonelline). Application of synthetic 3-carboxy-1-methyl pyridinium at high concentration (0.1 mM) also induced multiple firing and reduced voltage-activated K+ current. The changes in excitability of DRG neurones induced by 3-carboxy-1-methyl pyridinium suggest that this compound contributes to the bioactivity produced by the crude extracts from two soft corals.


CONCLUSIONS
Sarcophyton glaucum and Lobophyton crassum contain natural products including 3-carboxy-1-methyl pyridinium that increase the excitability of DRG neurones. We speculate that in addition to developmental control and osmoregulation these compounds may contribute to chemical defenses.
Temraz
Tarek A
TA
Marine Science Department, Suez Canal University, Ismailia, Egypt. ttemraz@yahoo.com
Houssen
Wael E
WE
Jaspars
Marcel
M
Woolley
David R
DR
Wease
Kerrie N
KN
Davies
Steven N
SN
Scott
Roderick H
RH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D037421:Anthozoa; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D019156:Indian Ocean; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology; D011726:Pyridinium Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011726:Pyridinium Compounds