Activation of nicotinic receptors triggers exocytosis from bovine chromaffin cells in the absence of membrane depolarization.
The traditional function of neurotransmitter-gated ion channels is to induce rapid changes in electrical activity. Channels that are Ca(2+)-permeable, such as N-methyl-D-aspartate receptors at depolarized membrane potentials, can have a broader repertoire of consequences, including changes in synaptic efficacy, developmental plasticity, and excitotoxicity. Neuronal nicotinic receptors for acetylcholine (nAChRs) are usually less Ca(2+)-permeable than N-methyl-D-aspartate receptors but have a significant Ca2+ permeability, which is greater at negative potentials. Here we report that in neuroendocrine cells, activation of nAChRs can trigger exocytosis at hyperpolarized potentials. We used whole-cell patch-clamp recordings to record currents and the capacitance detection technique to monitor exocytosis in isolated bovine chromaffin cells. Stimulation of nAChRs at hyperpolarized potentials (-60 or -90 mV) evokes a large current and a maximal capacitance increase corresponding to the fusion of approximately 200 large dense-core vesicles. The amount of exocytosis is controlled both by the Ca2+ influx through nAChRs and by a contribution from thapsigargin-sensitive Ca2+ sequestering stores. This is a form of neurotransmitter action in which activation of nAChRs triggers secretion through an additional coupling pathway that coexists with classical voltage-dependent Ca2+ entry.
Mollard
P
P
Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Seward
E P
EP
Nowycky
M C
MC
D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology
D011978:Receptors, Nicotinic; D013729:Terpenes; D019284:Thapsigargin; D009538:Nicotine; D000252:Calcium-Transporting ATPases; D002118:Calcium; D014403:Tubocurarine