| First Author | Lemtiri-Chlieh F | Year | 2022 |
| Journal | Am J Physiol Regul Integr Comp Physiol | PubMed ID | 35503519 |
| Mgi Jnum | J:325485 | Mgi Id | MGI:7281008 |
| Doi | 10.1152/ajpregu.00277.2021 | Citation | Lemtiri-Chlieh F, et al. (2022) The Hyperpolarization Activated, Cyclic Nucleotide Gated Channel Resides on Myocytes in Mouse Bladders and Contributes to Adrenergic-Induced Detrusor Relaxation. Am J Physiol Regul Integr Comp Physiol |
| abstractText | Control of urinary continence is predicated on sensory signaling about bladder volume. Bladder sensory nerve activity is dependent upon tension, implicating autonomic control over detrusor myocyte activity during bladder filling. HCN ion channels are known contributors to bladder control, but their mechanism of action is not well understood. The lack of a definitive identification of cell type(s) expressing HCN in the bladder presents a significant knowledge gap. We recently reported a complete transcriptomic atlas of the C57BL/6 mouse bladder showing the dominant HCN paralog in mouse bladder, Hcn1, is limited to a subpopulation of detrusor smooth myocytes (DSMs). Here, we report details of these findings, along with results of patch clamp experiments, immunohistochemistry, and functional myobath/tension experiments in bladder strips. Making use of a transgenic mouse expressing fluorescence-tagged alpha-smooth muscle actin, our data confirmed location and function of DSM HCN channels. Despite previous associations of HCN with postulated bladder interstitial cells, neither evidence of specific interstitial cell types nor an association of non-myocytes with HCN was discovered. We confirm that HCN activation participates in reducing sustained (tonic) detrusor tension via cAMP, with no effect on intermittent (phasic) detrusor activity. In contrast, blockade of HCN increases phasic activity induced by a protein kinase A (PKA) blocker or a large conductance Ca(2+)-activated K(+) (BK) channel opener. Our findings therefore suggest a central role for detrusor myocyte HCN in regulating and constraining detrusor myocyte activity during bladder filling. |
