| First Author | Zheng H | Year | 2023 |
| Journal | FASEB J | Volume | 37 |
| Issue | 5 | Pages | e22929 |
| PubMed ID | 37086093 | Mgi Jnum | J:341981 |
| Mgi Id | MGI:7541669 | Doi | 10.1096/fj.202201712R |
| Citation | Zheng H, et al. (2023) Cardiac PDGFRalpha(+) interstitial cells generate spontaneous inward currents that contribute to excitability in the heart. FASEB J 37(5):e22929 |
| abstractText | The cell types and conductance that contribute to normal cardiac functions remain under investigation. We used mice that express an enhanced green fluorescent protein (eGFP)-histone 2B fusion protein driven off the cell-specific endogenous promoter for Pdgfra to investigate the distribution and functional role of PDGFRalpha(+) cells in the heart. Cardiac PDGFRalpha(+) cells were widely distributed within the endomysium of atria, ventricle, and sino-atrial node (SAN) tissues. PDGFRalpha(+) cells formed a discrete network of cells, lying in close apposition to neighboring cardiac myocytes in mouse and Cynomolgus monkey (Macaca fascicularis) hearts. Expression of eGFP in nuclei allowed unequivocal identification of these cells following enzymatic dispersion of muscle tissues. FACS purification of PDGFRalpha(+) cells from the SAN and analysis of gene transcripts by qPCR revealed that they were a distinct population of cells that expressed gap junction transcripts, Gja1 and Gjc1. Cardiac PDGFRalpha(+) cells generated spontaneous transient inward currents (STICs) and spontaneous transient depolarizations (STDs) that reversed at 0 mV. Reversal potential was maintained when E(Cl) = -40 mV. [Na(+) ](o) replacement and FTY720 abolished STICs, suggesting they were due to a non-selective cation conductance (NSCC) carried by TRPM7. PDGFRalpha(+) cells also express beta(2) -adrenoceptor gene transcripts, Adrb2. Zinterol, a selective beta(2) -receptor agonist, increased the amplitude and frequency of STICs, suggesting these cells could contribute to adrenergic regulation of cardiac excitability. PDGFRalpha(+) cells in cardiac muscles generate inward currents via an NSCC. STICs generated by these cells may contribute to the integrated membrane potentials of cardiac muscles, possibly affecting the frequency of pacemaker activity. |
