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SK channels modulate firing frequency, calcium influx, and stress‐induced catecholamine secretion in mice.
Author(s) -
KolskiAndreaco Aaron,
Lotfipour Shahrdad,
Bond Chris,
Sailer Claudia,
GuntherKnaus Hans,
Leslie Frances,
Adelman John,
Chandy K. George
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a540-c
Subject(s) - catecholamine , secretion , calcium , endocrinology , chemistry , voltage dependent calcium channel , medicine , biophysics , neuroscience , biology
Small conductance Ca2+ activated K+ channels (SKCa) are well known modulators of neuronal excitability. We report the presence of SK channel subtypes SKCa2 and SKCa3 in adrenal chromaffin cells (ACCs) of the mouse adrenal medulla using immunhistostochemical and immunocytochemical detection. ACCs robustly expressing SKCa2 and SKCa3 also strongly expressed the enzyme phenylethanolamine‐N‐methytransferase (PNMT), which is responsible for the conversion of norepinephrine to epinephrine. Confirming the immunohistochemical data, SK currents were detected in ACCs and could be activated by calcium influx through voltage dependent calcium channels. Mouse ACCs exhibit both action potentials and calcium oscillations in culture, and application of SK channel inhibitors d‐tubocurarine, apamin, and Leiurotoxin, reversibly increased the action potential firing rate and enhance Ca2+ influx. Conversely the SK channel activator NS309 has opposing effects on action potential frequency and calcium influx. In addition, mice overexpressing either SKCa2 or SKCa3 (OE mice) possess ACCs with reduced action potential firing rates and calcium influx, with SKCa3 overexpressing mice showing more profound effects. Studies are underway to examine the levels of catecholamines in NS309‐treated, SKCa2‐OE, and SKCa3‐OE mice in response to stress, and evaluate the potential of SK channels as potential therapeutic targets for managing stress‐induced hypertension.