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Hyperpolarization and slowing of the rate of contraction in human uterus in pregnancy by prostaglandins E 2 and F 2α : involvement of the Na + pump
Author(s) -
Parkington Helena C.,
Tonta Mary A.,
Davies Nicola K.,
Brennecke S. P.,
Coleman H. A.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.229af.x
Subject(s) - hyperpolarization (physics) , depolarization , ouabain , membrane potential , chemistry , biophysics , isometric exercise , medicine , myometrium , nifedipine , excitatory postsynaptic potential , endocrinology , contraction (grammar) , calcium , biochemistry , sodium , uterus , biology , stereochemistry , receptor , organic chemistry , nuclear magnetic resonance spectroscopy
1 The effects of prostaglandins E 2 (PGE) and F 2α (PGF) on membrane potential and isometric tension and cytoplasmic free calcium concentration ([Ca 2+ ] i ) and tension were studied in strips of uterine smooth muscle obtained from women undergoing Caesarean delivery at term and during established labour. 2 Prostaglandins (PGs) evoked a biphasic response. The excitatory component consisted of depolarization of the membrane, which initiated spike action potentials, an increase in [Ca 2+ ] i and tension development. The membrane remained depolarized at −19 ± 1 mV for about 2 min, then repolarized abruptly, [Ca 2+ ] i promptly returned to basal levels, and tension development ceased. 3 This component of the response to PGE or PGF was followed by a slow hyperpolarization which reached −85 ± 2 mV ( n = 22 ) at term and −70 ± 2 mV ( n = 9 ) during labour, and during which spontaneous action potentials and tension development did not occur. 4 Nifedipine (10 −6 M) abolished spontaneous activity, abolished PG‐induced action potentials and reduced the increase in [Ca 2+ ] i (9 ± 3%, n = 6 ), the depolarization (10 ± 1 mV, n = 14 ), the tension (2 ± 1%, n = 14 ) and the hyperpolarization (9 ± 1 mV, n = 14 , at term). 5 A variety of K + channel blockers were without effect on the peak amplitude of the PG‐induced hyperpolarization but the latter did not occur in the presence of ouabain (10 −6 M) or in K + ‐free or low‐Na + solutions, suggesting an involvement of the Na + ‐K + ‐ATPase pump. 6 In conclusion, a substantial dependence on Ca 2+ influx through voltage‐operated Ca 2+ channels accounts for the importance of membrane potential in regulating contractions in human uterine smooth muscle. The classical excitatory effect of PGE and PGF is followed by hyperpolarization involving the Na + ‐K + ‐ATPase pump. The hyperpolarization restricts the response to a single contraction and decreases the frequency of subsequent contractions. The amplitude of the hyperpolarization decreases during labour, allowing contraction frequency to increase. Its persistence at this time ensures complete relaxation between each single robust contraction, preventing spasm of the uterus that would restrict blood flow to the fetus during delivery.