Nicotinic cholinergic modulation of voltage‐dependent calcium current in bovine adrenal chromaffin cells.

Abstract

SUMMARY1. The effects of cholinergic agonists on voltage-dependent calcium current (ICa) were studied in cultured chromaffin cells from bovine adrenal medulla.2. Application of both acetylcholine (ACh) and nicotine resulted in inward nicotinic current from a holding potential of -90 mV, and at the same time reversible decreases in depolarization-activated ICa. Both of these effects were blocked by d-tubocurarine, while atropine pre-treatment was ineffective.3. Internal accumulation of neither Na+ nor Ca2+ seems likely to explain the nicotinic-agonist-dependent decrease in ICa, as the modulation was observed with symmetrical Na+ solutions, with Ca2+-free Ba2+-containing external solutions, from holding potentials of both -90 and -40 mV, and when the internal Ca2+ buffer capacity was increased. 4. Isodihydrohistrionicotoxin, an open-channel blocker which does not compete for the agonist binding site, completely inhibited inward cholinergic currents while the agonist-dependent decrease in ICa was seen in only two of fifteen cells.5. The nicotinic agonist-mediated decreases in Icawere not voltage-dependent. 6. No changes in voltage-dependent INa were seen with the nicotinic agonists. 7. Muscarine, with or without GTP in the pipette solution, produced neither modulation of ICa nor any changes in steady holding currents. The nicotinic current and the reversible decrease in ICa induced by ACh and nicotine were not affected by including GTP, or the guanine nucleotide analogues GDP-/1-S and GTP-y-S, in the pipette solution.8. A 10 min pre-incubation of the cells in a high-K+ solution optimal for catecholamine secretion did not affect the nicotinic agonist-mediated decreases in