Characterization of cardiac microsomes from spontaneously hypertonic rats

Area of Science:

• Cardiovascular Physiology
• Cellular Biology
• Biochemistry

Background:

• Spontaneously hypertensive rats (SHR) exhibit cardiac hypertrophy and altered contractility.
• The sarcoplasmic reticulum Ca2+-ATPase (SERCA) is crucial for cardiac muscle relaxation by sequestering calcium ions.
• Dysfunction in calcium handling is implicated in various heart diseases.

Purpose of the Study:

• To investigate the capacity of Ca2+ sequestration in myocardial microsomes of SHR.
• To identify molecular alterations in the Ca2+ transport system associated with impaired contractility in SHR hearts.

Main Methods:

• Preparation of cardiac microsomal fractions from SHR and control rats.
• Assay of basal and extra Ca2+-ATPase activity.
• Measurement of initial and total Ca2+ uptake.
• Quantification of Ca2+ transport ATPase concentration using SDS-gel electrophoresis.
• Analysis of intramembranous particle density and phosphoprotein half-lives.

Main Results:

• Ca2+ sequestration capacity was significantly reduced (to 40% of control) in SHR hearts.
• Basal and extra Ca2+-ATPase activities were decreased.
• Initial and total Ca2+ uptake showed a similar reduction.
• Lower concentrations of Ca2+ transport ATPase, reduced intramembranous particle density, and increased phosphoprotein half-lives were observed.

Conclusions:

• The Ca2+ sequestering system in SHR hearts exhibits significant dysfunction.
• Impaired Ca2+ transport ATPase function and concentration contribute to reduced Ca2+ sequestration.
• This dysfunction of the Ca2+ sequestering system partially explains the altered contractility of hypertrophied myocardium in SHR.