Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active α1B-adrenoceptors

Abstract

The regulatory function of α 1B -adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na + /K + -ATPase and Ca 2+ -ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant α 1B -adrenoceptor (CAMα 1B -AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca 2+ -ATPase (PMCA) expression was increased by 30% in CAMα 1B -AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2) expression. Moreover, total Ca 2+ -ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na + /K + -ATPase activity nor the expression of α 1 and α 2 subunit isoforms was changed in CAMα 1B -AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac α 1B -AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.