The role of the sarcoplasmic reticulum in neonatal uterine smooth muscle: enhanced role compared to adult rat.
Little is known about contractile activity, response to agonists or excitation-contraction coupling in neonatal smooth muscle. We have therefore investigated 10-day rat uterus to better understand these processes, and compared it to adult uterus to elucidate how control of contractility develops. Spontaneous contractions are present in the 10-day neonatal uterus, although they are not as large or as regular as those present in adult tissues. External Ca(2+) entry via L-type Ca(2+) channels is the sole source of Ca(2+) and is essential for the spontaneous activity. The neonatal uterus was responsive to carbachol or prostaglandin F(2alpha) application; it showed a marked stimulation and a clear dissociation between the force and Ca(2+) changes. Such sensitization was not apparent in adult rat myometrium. The sarcoplasmic reticulum (SR) had more releasable Ca(2+) and contributed more to the response to agonists in neonatal compared to adult tissues. Thus, Ca(2+) entry as opposed to SR Ca(2+) release contributed much less to the uterine response to agonists in the neonatal, compared to adult tissues. Inhibition of the SR by cyclopiazonic acid also caused a more vigorous increase in Ca(2+) and contractile activity, particularly frequency, in the neonatal compared to the adult uterus. Taken together these data suggest that: (1) spontaneous activity is already present by day 10, (2) receptor-coupling and excitation-contraction signalling pathways are functional, (3) the SR and Ca(2+) sensitization mechanisms play a more prominent role in the neonate, and (4) there is a shift to a greater reliance on Ca(2+) entry and excitability with development of the myometrium.
Noble
Karen
K
Department of Physiology, The University of Liverpool, Liverpool L69 3BX, UK. knoble@liverpool.ac.uk
Wray
Susan
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D004791:Enzyme Inhibitors; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; D018721:Muscarinic Agonists; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid