Calcium-dependent currents in cultured rat dorsal root ganglion neurones are inhibited by an adenosine analogue.
Dorsal root ganglion neurones from 2-day-old rats were grown in dissociated culture. The effect of the adenosine analogue 2-chloroadenosine (2-CA) was investigated on action potential duration and on Ca2+ current (ICa) activation. 2-CA (0.5 microM) shortened both control action potentials and those prolonged by tetraethylammonium (TEA), Ba2+, or intracellular Cs+. This effect was prevented by two adenosine antagonists isobutylmethylxanthine (IBMX, 1-2 mM) and 8-phenyltheophylline (8-PT, 2.5 microM). The inward current, ICa, recorded using the 'whole-cell' patch-clamp technique in medium containing 2.5 microM-tetrodotoxin, 25 mM-TEA and 2.5 mM-Ba2+ was reduced by 2-CA (0.05 microM). The activation of ICa was decreased, but its reversal potential was unchanged. The effect of 2-CA was antagonized by IBMX (1 mM) and 8-PT (1 microM). 2-CA also reduced the large inward tail currents which occurred at the termination of the depolarizing voltage step command in a proportion of neurones. Brief application of 2-CA (0.05 microM) did not affect the inward holding current required to maintain the cells at -80 mV. In the presence of TTX (2.5 microM) and Ca2+ (5 mM), 2-CA decreased the activation of outward K+ currents caused by 5 s depolarizing voltage commands from -80 mV or -40 mV. The GABAB agonist (-)-baclofen (50-100 microM) also shortened the action potential duration and reduced ICa. 8-PT (1 microM) did not prevent the effect of baclofen on ICa. It is concluded that in cultured rat dorsal root ganglion neurones 2-CA reduces ICa activation by a direct effect on an A1 adenosine receptor.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015762:2-Chloroadenosine; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003864:Depression, Chemical; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D015762:2-Chloroadenosine; D019789:Tetraethylammonium; D013806:Theophylline; C028322:8-phenyltheophylline; D000262:Adenylyl Cyclases; D001418:Baclofen; D000241:Adenosine; D011188:Potassium; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine