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Voltage‐dependent inactivation of catecholamine secretion evoked by brief calcium pulses in the cat adrenal medulla.
Author(s) -
Garrido B,
López M G,
Moro M A,
de Pascual R,
García A G
Publication year - 1990
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1990.sp018231
Subject(s) - adrenal medulla , catecholamine , endocrinology , medicine , chemistry , secretion , perfusion , calcium , repolarization , electrophysiology , biology
1. Inactivation by voltage changes of 45Ca2+ uptake into and catecholamine release from cat adrenal glands perfused at a high rate (4 ml/min) at 37 degrees C with oxygenated Krebs‐Tris solution has been studied. Experimental conditions were selected so that adrenal medullary chromaffin cells were depolarized for different time periods and with various K+ concentrations in the absence of Ca2+, prior to the application of 0.5 mM‐Ca2+ for 10 s in the presence of 118 mM‐K+ to test the rate of secretion (the ‘Ca2+ pulse’). 2. Application of the Ca2+ pulse after perfusion with 5.9 mM‐K+ led to a 100‐fold increase of the basal rate of secretion. However, if the Ca2+ pulse was preceded by a 10 min period of perfusion with 118 mM‐K+, the secretory response was decreased by over 80%. 3. Inactivation of secretion starts 10‐30 s after high‐K+ perfusion and is completed 2‐5 min thereafter. Inactivation is readily reversed by perfusing the glands with normal K(+)‐containing solution; the recovery phenomenon is also gradual and time‐dependent, starting 30 s after repolarization and ending 300 s thereafter. 4. The rate of inactivation is much slower at 35 than at 118 mM‐K+, suggesting that the process is strongly dependent on voltage. 5. Like catecholamine release, Ca2+ uptake into adrenal medullary chromaffin cells is inactivated in a voltage‐dependent manner. This, together with the fact that Cd2+ blocked secretion completely and inactivation was seen equally using Ca2+ or Ba2+ as secretagogues, suggests that inactivation of a certain class of voltage‐dependent Ca2+ channels is responsible for the blockade of secretion. Such channels must be slowly inactivated by voltage and highly sensitive to dihydropyridines, since (+)PN200‐110 (an L‐type Ca2+ channel blocker) enhanced the rate of inactivation and (+/‐)Bay K 8644 (an L‐type Ca2+ channel activator) prevented it, indicating that they might belong to L‐subtype Ca2+ channels. 6. The effects of (+/‐)Bay K 8644 (100 nM) were seen on both the voltage and time dependence of inactivation. At a moderate depolarization (35 mM‐K+), the drug prevented inactivation and caused potentiation of secretion which developed gradually; at strong depolarizations (118 mM‐K+), Bay K 8644 prevented the time‐dependent development of inactivation. (+)PN200‐110 (30 nM) did not suddenly decrease catecholamine release at the earlier times of depolarization; what the drug did was to accelerate the normal rate of inactivation induced by depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)