This preclinical study demonstrates significant developmental changes in muscarinic potassium current density and receptor sensitivity in rat atrial myocytes from fetal to adult stages.
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Maturation of muscarinic K+ currents occurs in developing rat atria; extends preclinical understanding but leaves open clinical translation.
Single atrial myocytes were isolated from fetal, neonatal, and adult rat hearts. The muscarinic K+ current activated by rapid application of acetylcholine (ACh) and adenosine (Ado) was recorded under the whole cell voltage clamp. The current density (pA/pF) of ACh-induced K+ current increased from gestation day 12 to the maximum on neonatal day 20 and decreased in the adult myocytes due to greater increase of the membrane capacitance. The development of Ado-induced K+ current followed a similar time course except for a remarkable decrease after neonatal day 10. No significant change was found in single-channel properties during the development. Receptor subtypes were M2 and A1 receptors for ACh and Ado, respectively. In the dose-response relationship, the half-maximal concentration for ACh-induced current markedly decreased with age, from 1.44 (fetus) to 0.17 microM (adult), whereas that for Ado increased from 0.45 (fetus) to 0.99 microM (adult). These changes of the muscarinic K+ current were discussed in relation to the functional development of cardiac myocytes and underlying mechanisms.
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Takano et al. (1997) studied this question.
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