Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders.
Sheep fetus is a useful model to study in utero bladder outflow obstruction but little is known about cell physiology of fetal bladders. To remedy this defect we have characterised intracellular Ca(2+) regulation in fetal sheep myocytes of different developmental ages. Fetal detrusor myocytes had a similar resting [Ca(2+)](i) to adult cells and exhibited transient [Ca(2+)](i) increases in response to carbachol, ATP, high-K, caffeine and low-Na. The carbachol transients were abolished by atropine and caffeine; the ATP response was blocked by alpha,beta-methylene ATP; high-K-evoked [Ca(2+)](i) rises were antagonised by verapamil. The maximal responses to carbachol, high-K, caffeine and low-Na in fetal cells were similar to those of adult counterparts, whilst the ATP response was smaller (p < 0.05). These variables were largely similar between the three gestational groups with the exception of ATP-induced response between early fetal and adult bladders (p < 0.05). Dose-response curves to carbachol demonstrated an increase of potency between mid-gestation and early adulthood (p < 0.05). These data show that muscarinic receptors coupled to intracellular Ca(2+) release, P2X receptor-linked Ca(2+) entry, depolarisation-induced Ca(2+) rise via L-type Ca(2+) channels, Na(+)/Ca(2+) exchange and functional intracellular Ca(2+) stores are all operational in fetal bladder myocytes. Whilst most of Ca(2+) regulators are substantially developed and occur at an early fetal age, a further functional maturation for cholinergic sensitivity and purinergic efficacy continues throughout to adulthood.
Department of Medicine, University College London, UK. c.wu@ucl.ac.uk
C
C
Wu
G
G
Sui
N
N
Thiruchelvam
P
P
Cuckow
C H
CH
Fry
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000502:physiology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D032342:Muscle Cells / Q000502:physiology*; D009130:Muscle, Smooth / Q000196:embryology / Q000378:metabolism*; D012756:Sheep; D001743:Urinary Bladder / Q000196:embryology / Q000378:metabolism / Q000502:physiology*
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D018679:Cholinergic Agonists; D002110:Caffeine; D000255:Adenosine Triphosphate; D002217:Carbachol; D002118:Calcium