| First Author | Sebastian S | Year | 2013 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 305 |
| Issue | 4 | Pages | R435-42 |
| PubMed ID | 23697798 | Mgi Jnum | J:198997 |
| Mgi Id | MGI:5500095 | Doi | 10.1152/ajpregu.00037.2013 |
| Citation | Sebastian S, et al. (2013) The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins. Am J Physiol Regul Integr Comp Physiol 305(4):R435-42 |
| abstractText | Reciprocal physiological modulation of heart rate is controlled by the sympathetic and parasympathetic systems acting on the sinoatrial (SA) node. However, there is little direct in vivo work examining the role of stimulatory and inhibitory G protein signaling in the SA node. Thus, we designed a study to examine the role of the stimulatory (Galphas) and inhibitory G protein (Galphai2) in in vivo heart rate regulation in the SA node in the mouse. We studied mice with conditional deletion of Galphas and Galphai2 in the conduction system using cre-loxP technology. We crossed mice in which cre recombinase expression was driven by a tamoxifen-inducible conduction system-specific construct with "Galphas floxed" and "Galphai2 floxed" mice. We studied the heart rate responses of adult mice compared with littermate controls by using radiotelemetry before and after administration of tamoxifen. The mice with conditional deletion of Galphas and Galphai2 had a loss of diurnal variation and were bradycardic or tachycardic, respectively, in the daytime. In mice with conditional deletion of Galphas, there was a selective loss of low-frequency power, while with deletion of Galphai2, there was a loss of high-frequency power in power spectral analysis of heart rate variability. There was no evidence of pathological arrhythmia. Pharmacological modulation of heart rate by isoprenaline was impaired in the Galphas mice, but a muscarinic agonist was still able to slow the heart rate in Galphai2 mice. We conclude that Galphas- and Galphai2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system. |
