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17 Changes in the Role of the SR in SAN Function Across the Lifespan May Be responsible for Changing Pacemaker Stability and Response
  1. Fiona Hatch,
  2. K Matthew
  1. Lancaster, Sandra A. Jones. Dept. Biological Sciences & HYMS, University of Hull, Kingston-upon-Hull, HU6 7RX, U.K. and *Faculty of Biological Sciences, University of Leeds, LS29JT, U.K

Abstract

Background Intracellular calcium regulation is important for regulating sinoatrial node (SAN) activity. Ventricular expression of the sarcoendoplasmic recticulum (SR) Ca-ATPase pump (SERCA) has been shown to decline with age; a change which if repeated in the SAN may contribute to the well-documented decline in SAN activity, stability and response with advanced age.

Method Male Wistar rats at 6 months (young), 12 months (adult) and 24 months (old) (n=5 per group) were killed by a Home Office approved. The SAN region of the heart was dissected and maintained in bicarbonate-buffered saline at 37°C. Intrinsic pacemaker activity was recorded under control conditions and in the presence of 3µMM cyclopiazonic acid (CPA) to inhibit SERCA. Western blot was used to assess expression of SERCA and the SR calcium-release channel, the ryanodine receptor RYR2, both shown expressed relative to levels in the young SAN. Data are shown as mean ± SEM.

Results Intrinsic SAN beating rate significantly decreased in old age (young 260±17bpm vs. old 216±15bpm; P=0.04). CPA caused slowing in both young and adult SAN by 26±9 and 49±10bpm respectively (P=0.001), but not in the old SAN. SERCA2a and RYR2 expression increased from young to adult (SERCA young 100±9.8% vs. adult 135±10.8%; P=0.002: RYR2 young 100±21.9% vs. 152±11.2%; p=0.0006), but declined substantially in old age to levels below the young (SERCA old 72±11.7%; RYR2 old 53±4.3%).

Conclusion The data show a diminished SR influence on pacemaking in the old SAN. In contrast developmentally the SR may increase its pacemaker role from young to adult animals.

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