title: Localized secretion of ATP and opioids revealed through single Ca2+ channel modulation in bovine chromaffin cells.
abstract: In bovine chromaffin cells, the Ca2+ channels involved in exocytosis are effectively inhibited by ATP and opioids that are coreleased with catecholamines during cell activity. This autocrine loop causes a delay in Ca2+ channel activation that is quickly removed by preceding depolarizations. Changes in Ca2+ channel gating by secreted products thus make it possible to correlate Ca2+ channel activity to secretory events. Here, using cell-attached patch recordings, we found a remarkable correlation between delayed Ca2+ channel openings and neurotransmitter secretion induced by either local or whole-cell Ba2+ stimulation. The action is specific for N- and P/Q-type channels and largely prevented by PTX and mixtures of purinergic and opioid receptor antagonists. Overall, our data provide evidence that exocytosis, viewed through the autocrine inhibition of non-L-type channels, is detectable in membrane patches of approximately 1 microm2 distributed over 30%-40% of the total cell surface, while Ca2+ channels and autoreceptors are uniformly distributed over most of the cell membrane.
authors.affiliation: Department of Neuroscience, I.N.F.M. Research Unit, Turin, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Carabelli
authors.forename: I
authors.initials: I
authors.lastname: Carra
authors.forename: E
authors.initials: E
authors.lastname: Carbone
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019898:Autocrine Communication / Q000502:physiology; D001464:Barium / Q000493:pharmacokinetics; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D002417:Cattle; D019439:Chromaffin Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005089:Exocytosis / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
chemical_list: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D000700:Analgesics; D000701:Analgesics, Opioid; D000970:Antineoplastic Agents; D001464:Barium; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins; D009270:Naloxone; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D009543:Nifedipine; D018847:Opioid Peptides; D010455:Peptides; D011957:Receptors, Opioid; D011983:Receptors, Purinergic; D013111:Spider Venoms; D013498:Suramin; D010566:Virulence Factors, Bordetella; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA