Inhibition of Calcium Currents by an Adenosine Analogue 2-Chloroadenosine

Abstract

The mechanism of inhibition of calcium currents (lca) by the adenosine analogue 2-chloroaden-osine (2-CA) has been studied in cultured rat dorsal root ganglion (drg) neurones. The low-threshold inward current activated by small depolarising steps was less sensitive to 2-CA than the large high-threshold Ica activated at about 0 mV. The adenosine receptor antagonists 8-phenyltheophylline (8-PT) and isobutylmethylxanthine (IBMX) selectively blocked the inhibition of ICa by 2-CA but had no effect on its inhibition by the GABAB agonist baclofen. 2-CA also inhibited both the calcium-dependent potassium current (IK(Ca)) and the voltage-dependent transient potassium current(IK(vt),indicating that the inhibition of ICa by 2-CA was not secondary to an increase in outward potassium currents. This was supported by the observation that the ability of 2-CA to inhibit ICa was not reduced by 4-aminopyridine. The action of 2-CA on a second calcium-dependent current believed to be IC1(Ca) was also studied. Like IK(Ca) ICI(Ca) was markedly reduced by 2-CA. The involvement of a guanine nucleotide-binding protein in coupling the adenosine receptor to Ca2+ channels was investigated, by inclusion of the GTP analogue guanosine 5′-0-3-thiotriphosphate (GTP-γ-S) and the GDP analogue guanosine 5′-0-2-thiodiph-osphate (GDP-s-S) in the internal solution. GTP-γ-S enhanced and GDP-s-S reduced the inhibition of ICa by 2-CA.