Circadian expressions of cardiac ion channel genes in mouse might be associated with the central clock in the SCN but not the peripheral clock in the heart

Abstract

Significant circadian variations exist in the frequency of cardiac arrhythmia, but few studies have examined the relation between cardiac ion channels genes and biological clocks. We investigated this relation using suprachiasmatic nuclei lesion (SCNX) and pharmacological autonomic nervous system block (ANSB) mice. Significant 24-h variations were observed in the expression of clock genes Per2, Bmal1, and Dbp and ion channel genes KCNA5, KCND2, KCHIP2, and KCNK3 in the control mice hearts. In the SCNX mice, all genes examined lost circadian rhythm. In the ANSB mice, the expressions of the three clock genes were dampened significantly but still had circadian rhythm, whereas the four ion channel gene expressions lost rhythm. Heart rate also lost circadian rhythm in both the SCNX and ANSB mice. These results suggest that some ion channel gene expressions might be regulated by the central clock in the SCN through the ANS but not the peripheral clock in the heart.

Effect of eicosapentaenoic acid and pitavastatin on electrophysiology and anticoagulant gene expression in mice with rapid atrial pacing

“…2). The surface ECG was recorded using a DSI Dataquest A.R.T.2.3 system at a sampling rate of 1 kHz (Data Sciences International, St. Paul, MN, USA) with a telemetry transmitter fixed on the mice as described previously (23). After 8 h of pacing, the left atrial appendages were harvested within 30 sec and the tissues were immediately frozen in liquid nitrogen for subsequent RNA isolation.…”

Circadian control of intrinsic heart rate via a sinus node clock and the pacemaker channel

“…Some circadian varying ion channels are common to the sinus node and the atrial or ventricular muscle: Na v 1.5 ( Scn5a ), K v 4.2 ( Kcnd2 ), K v 1.5 ( Kcna5 ), ERG (K v 11.1; Kcnh2 ) and TASK-1 (K2p3.1; Kcnk3 ). Of these, all were significantly more highly expressed at ZT 12 than ZT 0 in the sinus node (Figure 2G); in atrial and ventricular muscle, there was a qualitatively similar circadian rhythm in Na v 1.5 ( Scn5a ) 46 , K v 4.2 ( Kcnd2 ) 41,43,48 , K v 1.5 ( Kcna5 ; in ventricular muscle, but not atrial muscle) 41,43 and ERG (K v 11.1; Kcnh2 ) 48 . However, the opposite circadian rhythm in TASK-1 (K2p3.1; Kcnk3 ) has been reported in atrial and ventricular muscle 41 .…”

“…In atrial muscle, a circadian rhythm has been reported in K v 4.2 ( Kcnd2 ) 41,43,44 , KChIP2 ( Kcnip2 ) 41,44 , K v 1.5 ( Kcna5 ) 41,43 , TASK-1 (K2p3.1; Kcnk3 ) 41 , Cx40 ( Gja5 ) 45 and Cx43 ( Gja1 ) 45 . In ventricular muscle, a circadian rhythm has been reported in Na v 1.5 ( Scn5a ) 46 , Ca v 1.2 ( Cacna1c ) 47 , K v 4.2 ( Kcnd2 ) 41,43,48 , KChIP2 ( Kcnip2 ) 41,44 , K v 1.5 ( Kcna5 ) 41,43 , ERG (K v 11.1; Kcnh2 ) 48 , TASK-1 (K2p3.1; Kcnk3 ) 41 , Cx40 ( Gja5 ) 45 and Cx43 ( Gja1 ) 45 . Some circadian varying ion channels are common to the sinus node and the atrial or ventricular muscle: Na v 1.5 ( Scn5a ), K v 4.2 ( Kcnd2 ), K v 1.5 ( Kcna5 ), ERG (K v 11.1; Kcnh2 ) and TASK-1 (K2p3.1; Kcnk3 ).…”

“…Previously, it has been demonstrated that there a functioning circadian clock in the heart e.g 41. .…”

“…This study has demonstrated that Hcn4 is likely to be under the control of BMAL1 generated by the local clock (Figure 6). In the ventricle, it has been reported that: Na v 1.5 ( Scn5a ) and ERG (K v 11.1; Kcnh2 ) are under the control of CLOCK:BMAL1 generated by the local clock 46,48 ; and K v 4.2 ( Kcnd2 ), K v 1.5 ( Kcna5 ), TASK-1 (K2p3.1; Kcnk3 ), Cx40 ( Gja5 ) and Cx43 ( Gja1 ) are under the control of the suprachiasmatic nucleus (not the local clock) via the autonomic nervous system 41 . Confusingly, KChIP2 ( Kcnip2 ) has been reported to be under the control of a BMAL1-dependent (i.e.…”