Role of Inositol 1, 4, 5-Triphosphate on Heart Rate in Isolated Heart Models of Wistar Rats

Jesi, W (2015) Role of Inositol 1, 4, 5-Triphosphate on Heart Rate in Isolated Heart Models of Wistar Rats. Masters thesis, Christian Medical College, Vellore.


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The sodium calcium exchanger (NCX) is emerging as the primary pacemaking mechanism in heart. It extrudes 1 Calcium ion for 3 Sodium ions taken into the cell (forward mode of NCX), thereby producing an inward current which depolarizes the cell. Calcium should be available in cytoplasm to drive NCX in forward mode. Diastolic calcium release from sarcoplasmic reticulum (SR) provides for calcium to drive forward NCX. But the route(s) of calcium release from SR is/are to be confirmed. In this study we wanted to see the role of Inositol1, 4, 5-triphosphate receptor (IP3R) in diastolic calcium release. If it is involved, stimulating IP3R should increase heart rate and decreasing IP3 formation should decrease heart rate. In this study rat hearts were isolated and perfused with normal extracellular solution in Langendorff mode and the heart rate was recorded. Phenylephrine, an IP3 agonist was added to the perfusate and its effect on heart rate was recorded (n=6). Neomycin which blocks the production of IP3 was added along with Phenylephrine in another set of experiments and the effects on heart rate was recorded (n=6). The change in heart rate was compared and analysed using Wilcoxon Signed Rank test. Our results showed a 44% increase in heart rate with Phenylephrine (p = 0.028). With Neomycin the Phenylephrine-induced increase in heart rate was blocked. This confirms that the positive chronotropic effect of Phenylephrine is through IP3. The study confirms that IP3 has a positive chronotropic effect. This opens a whole new portal of pharmaco-therapeutics in the management of cardiovascular pathologies like arrhythmias.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Inositol 1, 4, 5-Triphosphate ; Heart Rate ; Isolated Heart Models ; Wistar Rats.
Subjects: MEDICAL > Physiology
Depositing User: Punitha K
Date Deposited: 24 May 2018 17:49
Last Modified: 27 May 2018 11:30

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