Thyroid hormone, particularly the biologically active triiodothyronine (T3), exerts profound effects on the heart by increasing heart rate (positive chronotropic effect) and enhancing the force of contraction (positive inotropic effect). These effects are mediated through genomic actions that modulate gene expression and protein synthesis, resulting in changes in cardiac muscle physiology.

Evaluation of the Proposed Statements on T3 Cardiac Effects

• A. T3 inhibits α-myosin heavy chain gene expression and enhances β-myosin heavy chain expression.
  This is incorrect. T3 actually increases expression of α-myosin heavy chain (MHCα), which has higher ATPase activity and faster contraction characteristics, and inhibits β-myosin heavy chain (MHCβ) gene expression which encodes slower contractile proteins.pmc.ncbi.nlm.nih

• B. Expression of gene for Na+-Ca++ antiporter is enhanced by T3.
  This is correct. T3 upregulates the Na+-Ca++ exchanger, which assists in calcium extrusion from myocytes during relaxation, contributing to improved diastolic function.pmc.ncbi.nlm.nih

• C. Sarcoplasmic reticulum Ca++ ATPase (SERCA) expression is increased by T3.
  This is correct. T3 increases SERCA levels, enhancing calcium reuptake into the sarcoplasmic reticulum during diastole, improving relaxation and contractility.pmc.ncbi.nlm.nih

• D. T3 increases ryanodine receptor Ca++ channel in the sarcoplasmic reticulum.
  This is correct. T3 enhances the expression and function of ryanodine receptors, facilitating calcium release during systole and strengthening contractions.pmc.ncbi.nlm.nih

• E. T3 inhibits the number of β-adrenergic receptors in heart muscle.
  This is incorrect. T3 increases β1-adrenergic receptor expression, improving responsiveness of the heart to sympathetic stimulation.pmc.ncbi.nlm.nih

Correct Combinations Based on Above

From the provided options:

• (1) A and B → Incorrect (A wrong)

• (2) B and C → Correct (B and C are correct)

• (3) C and D → Also Correct (C and D are correct)

• (4) D and E → Incorrect (E wrong)

Both (2) B and C and (3) C and D contain correct statements. However, since C (SERCA increase) is common in both and D (ryanodine receptor increase) is specifically associated with calcium release enhancement, the best choice emphasizing calcium handling improvement is:

(3) C and D

Detailed Explanation of Mechanisms

• Myosin Heavy Chain Isoform Regulation: T3 shifts expression towards the α-MHC isoform, increasing contractility efficiency and speed.

• Calcium Handling Proteins:

  • Upregulation of SERCA accelerates calcium sequestration into the sarcoplasmic reticulum during diastole, facilitating relaxation.

  • Increased ryanodine receptor expression improves calcium release during systole, enhancing contraction strength.

  • Enhanced Na+-Ca++ exchanger helps maintain calcium homeostasis.

• Adrenergic Sensitivity: Increased β1-adrenergic receptor density amplifies the heart’s response to sympathetic stimulation, boosting heart rate and contractility.

Summary Table

Conclusion

The combination best reflecting correct molecular effects of T3 on the heart is:

(3) C and D