Open AccessHyperpolarization‐activated cyclic nucleotide‐gated channels working as pacemaker channels in colonic interstitial cells of Cajal
Author(s) -
Choi Seok,
Seo Hyunhyo,
Lee Kyungmin,
Shin Dong Hoon,
Wu Mei Jin,
Wu Wenhao,
Huang Xingyou,
Zhang Jingwei,
Hong Chansik,
Jun Jae Yeoul
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17087
Subject(s) - interstitial cell of cajal , hcn channel , pacemaker potential , hyperpolarization (physics) , medicine , phosphodiesterase , cyclase , endocrinology , adenylate kinase , chemistry , membrane potential , electrophysiology , biology , ion channel , microbiology and biotechnology , biophysics , receptor , biochemistry , stimulation , enzyme , organic chemistry , smooth muscle , nuclear magnetic resonance spectroscopy
Hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels function as pacemaker channels in spontaneously active cells. We studied the existence of HCN channels and their functional roles in the interstitial cells of Cajal (ICC) from the mouse colon using electrophysiological, immunohistochemical and molecular techniques. HCN1 and HCN3 channels were detected in anoctamin‐1 (Ca 2+ ‐activated Cl − channel; ANO1)‐positive cells within the muscular and myenteric layers in colonic tissues. The mRNA transcripts of HCN1 and HCN3 channels were expressed in ANO1‐positive ICC. In the deletion of HCN1 and HCN3 channels in colonic ICC, the pacemaking potential frequency was reduced. Basal cellular adenylate cyclase activity was decreased by adenylate cyclase inhibitor in colonic ICC, whereas cAMP‐specific phosphodiesterase inhibitors increased it. 8‐Bromo‐cyclic AMP and rolipram increased spontaneous intracellular Ca 2+ oscillations. In addition, Ca 2+ ‐dependent adenylate cyclase 1 (AC1) mRNA was detected in colonic ICC. Sulprostone, a PGE 2 ‐EP 3 agonist, increased the pacemaking potential frequency, maximum rate of rise of resting membrane in pacemaker potentials and basal cellular adenylate cyclase activity in colonic ICC. These results indicate that HCN channels exist in colonic ICC and participate in generating pacemaking potentials. Thus, HCN channels may be therapeutic targets in disturbed colonic motility disorders.