Pituitary adenylate cyclase-activating peptide (PACAP) recruits low voltage-activated T-type calcium influx under acute sympathetic stimulation in mouse adrenal chromaffin cells.
Low voltage-activated T-type Ca(v)3.2 calcium channels are expressed in neurosecretory chromaffin cells of the adrenal medulla. Previous studies have shown that naïve adrenal chromaffin cells express a nominal Ca(v)3.2-dependent conductance. However, Ca(v)3.2 conductance is up-regulated following chronic hypoxia or long term exposure to cAMP analogs. Thus, although a link between chronic stressors and up-regulation of Ca(v)3.2 exists, there are no reports testing the specific role of Ca(v)3.2 channels in the acute sympathoadrenal stress response. In this study, we examined the effects of acute sympathetic stress on T-type Ca(v)3.2 calcium influx in mouse chromaffin cells in situ. Pituitary adenylate cyclase-activating peptide (PACAP) is an excitatory neuroactive peptide transmitter released by the splanchnic nerve under elevated sympathetic activity to stimulate the adrenal medulla. PACAP stimulation did not evoke action potential firing in chromaffin cells but did cause a persistent subthreshold membrane depolarization that resulted in an immediate and robust Ca(2+)-dependent catecholamine secretion. Moreover, PACAP-evoked secretion was sensitive to block by nickel chloride and was acutely inhibited by protein kinase C blockers. We utilized perforated patch electrophysiological recordings conducted in adrenal tissue slices to investigate the mechanism of PACAP-evoked calcium entry. We provide evidence that stimulation with exogenous PACAP and native neuronal stress stimulation both lead to a protein kinase C-mediated phosphodependent recruitment of a T-type Ca(v)3.2 Ca(2+) influx. This in turn evokes catecholamine release during the acute sympathetic stress response.
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
Jacqueline
J
Hill
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
Shyue-An
SA
Chan
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
Barbara
B
Kuri
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106. Electronic address: Corey.Smith@Case.Edu.
Corey
C
Smith
D000313:Adrenal Medulla / Q000166:cytology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000737:chemistry; D002395:Catecholamines / Q000378:metabolism; D019439:Chromaffin Cells / Q000166:cytology*; D004594:Electrophysiology / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D009532:Nickel / Q000737:chemistry; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D013564:Sympathetic Nervous System
C504883:Cacna1h protein, mouse; D020747:Calcium Channels, T-Type; D002395:Catecholamines; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D009532:Nickel; D011493:Protein Kinase C; D002118:Calcium