Effects of 2-chloroadenosine on electric potentials in brain synaptic membrane vesicles.

Isolated synaptic plasma membrane vesicles developed an internal negative membrane potential (delta psi) following loading with potassium succinate and incubation in NaCl, sodium succinate, or Tris succinate media. Membrane delta psi was monitored by measuring triphenyl[3H]methylphosphonium ion ([3H]TPMP+) accumulation by these vesicles. Estimates of delta psi ranged from --6.9 mV for vesicles incubated in sodium succinate to --28 mV for membranes incubated in NaCl. Intravesicular TPMP+ accumulation was strongly dependent on the K+ diffusion potential and was enhanced by the K+ ionophore valinomycin and by the adenosine analog 2-chloroadenosine (2-Cl-Ado). The stimulation of TPMP+ influx by 2-Cl-Ado was dependent on the concentration of this agent, independent of Cl- fluxes, and sensitive to inhibition by the methylxanthine theophylline. The increase of delta psi of the synaptic membrane vesicles caused by 2-Cl-Ado paralleled the hyperpolarization of neurons produced by adenosine and 2-Cl-Ado in physiological systems.