title: Cardiac-directed expression of adenylyl cyclase and heart rate regulation.
abstract: Mice with cardiac-directed overexpression of AC(VI) show increased cardiac responsiveness to beta-adrenergic receptor stimulation but regulation of heart rate is unknown. Telemetry was used to test the hypothesis that mice overexpressing cardiac adenylyl cyclase type VI (AC(VI)) would have normal heart rate regulation. Mice overexpressing cardiac AC(VI) were generated using the alphaMHC promoter and studied 10 days after implantation of telemetry devices. Cardiac transgene AC(VI) presence and expression was verified using PCR, RT-PCR and immunoblotting. Ambulatory heart rates were assessed using time and frequency domain analysis over two 24 hour light-dark cycles. Heart rates then were assessed following pharmacological blockade. Time domain analyses showed ambulatory heart rates were unchanged (AC(VI): 597 +/- 15 (SEM) bpm, Control: 595 +/- 12 bpm; p = 0.92). Circadian heart rate variability was preserved and not different from control mice (ANOVA, p = 0.52). Frequency domain analysis of heart rate variability also was unchanged. No difference in heart rate response to pharmacological autonomic blockade was found (intrinsic heart rate: AC(VI) 622 +/- 17 bpm, control 616 +/- 16 bpm, p = 0.79). In conclusion, mice overexpressing cardiac AC(VI) have normal conscious ambulatory heart rates and normal heart rate variability. Overexpression of cardiac AC(VI) does not result in altered heart rate regulation in contrast to cardiac overexpression of other elements of the beta-adrenergic signaling pathway.
authors.affiliation: VA Medical Center (125), 3350 La Jolla Village Drive, San Diego, CA 92161, USA. droth@ucsd.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Drumm
authors.forename: Valmik
authors.initials: V
authors.lastname: Bhargava
authors.forename: James S
authors.initials: JS
authors.lastname: Swaney
authors.forename: Mei Hua
authors.initials: MH
authors.lastname: Gao
authors.forename: H Kirk
authors.initials: HK
authors.lastname: Hammond
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology*; D009928:Organ Specificity; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001285:Atropine; D011433:Propranolol; D000262:Adenylyl Cyclases