Calcium-dependent currents in cultured rat dorsal root ganglion neurones are inhibited by an adenosine analogue

Abstract

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.