Functional remodeling of arterial tone regulation in postnatal development: switch of the leading potassium channels from less to more calcium-dependent channel typesтезисы докладаТезисы
Аннотация:Introduction: After birth the mammalian circulatory system undergoes crucial structural and functional alterations associated with a strong increase of systemic blood pressure. Thus, a considerable remodeling of the mechanisms responsible for vascular smooth muscle contraction has been observed with a switch away from mechanisms weakly dependent on changes in the intracellular calcium concentration (calcium sensitization) in the newborn towards more calcium-dependent mechanisms in adults. Vascular smooth muscle cells express a variety of potassium channels. These channels contribute to many signaling pathways that mediate vessel contraction and dilation. Whether the functional role of potassium channels also undergoes remodeling after birth has not been studied systematically. Therefore, the hypothesis was studied that vascular smooth muscle potassium channels undergoa switch from less to more calcium-dependent channel types.Methods and Material: Saphenous arteries from young (10- to 15-day old) and adult (2- to 3-month old) male rats have been studied using qPCR, digital PCR, Western blotting, isometricmyography, sharp microelectrodes and arterial blood pressure measurements under urethane anaesthesia.Results: Blockers of Kv1, Kir2, Kv7 and TASK-1 channels (DPO-1, BaCl₂, XE991, AVE1231) induced an enhancement of methoxamine-induced contraction that was larger in arteries of young compared to adult animals. In contrast, the BK channelblocker iberiotoxin had a stronger influence in adult rats. Blockers of KATP and Kv2 channels (glibenclamide, stromatoxin) had similar, not pronounced effects at both ages. The larger influence of Kv7, Kir2 and TASK-1 channel blockade on arterial contraction in young rats was associated with more prominent smooth muscledepolarization. The observed alterations in potassium channel functioning were consistent with differences in their mRNA and protein expression in arterial smooth muscle. In addition, intravenous administration of AVE1231 did not affect mean arterial pressure in adult but prominently increased it in young rats.Conclusion: These data show that vascular smooth muscle potassium channel expression and functioning changes considerably after birth. Thus, negative feedback regulation of vasocontraction is dominated by less calcium-dependent potassium channel types – Kv1, Kv7, TASK-1 and Kir2 – right after birth, whereas itis governed by the calcium-dependent BK channel later in life.
