The Role of Membrane Potential in the Control of Uterine Motility

117

The intracellular calcium concentration ([Ca2+]i) was measured at 35 °C using the fluorescent indicator indo‐1 in patch‐clamped, single uterine myocytes from pregnant rats to investigate the relationship between depolarization, Ca2+ current (ICa) and [Ca2+]i. Membrane depolarization activated ICa and produced a [Ca2+]i transient. The rapid increase in [Ca2+]i occurred at the same time as the inward ICa. Both ICa and the increase in [Ca2+]i were abolished by nifedipine (10 μm). When the membrane potential was held at ‐80 mV the threshold depolarization for an increase in [Ca2+]i was about ‐55 to ‐50 mV. As the magnitude of the depolarization was increased to about 0 mV there was an increase in the size of both ICa and the increase in [Ca2+]i. As the magnitude of the depolarization was further increased both ICa and the [Ca2+]i increase declined. When the depolarizing pulses were applied at 3 Hz to mimic normal action potentials then the individual [Ca2+]i transients did not fully relax and a tetanic rise of [Ca2+]i was observed. Under these conditions, there was not a simple relationship between the magnitude of the Ca2+ response and Ca2+ entry. When pairs of depolarizing pulses were applied, the increase in [Ca2+]i produced by the second pulse was larger (in relation to the magnitude of the L‐type Ca2+ current) than that produced by the first pulse. This facilitation was abolished by both ryanodine and cyclopiazonic acid suggesting a role for release from intracellular stores. We conclude that the L‐type Ca2+ current is the major source of Ca2+ ions entering the cell to produce the [Ca2+]i transient on depolarization. The magnitude of the increase in [Ca2+]i may, however, be amplified by Ca2+‐induced Ca2+ release.

Section: Physiological Significancesupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Properties of voltage‐activated [Ca²⁺]_i transients in single smooth muscle cells isolated from pregnant rat uterus

Shmigol

Eisner

Wray

1998

117

“…During each contraction a burst of action potentials is observed subsequent to slow depolarization, which is thought to be the pacemaker potential (Parkington & Coleman, 1990 (Kasai et al 1994b). Therefore, Ca2+ influx during action potentials seems to be the major source of [Ca2+]i rise associated with the rhythmic contractions.…”

Section: Discussionmentioning

confidence: 99%

Stretch‐induced enhancement of contractions in uterine smooth muscle of rats.

Kasai

Tsutsumi

Taketani

et al. 1995

1. We studied the effect of servo-controlled stretch of smooth muscle strips from rat uterus on tension and intracellular Ca2+ concentration ([Ca2+]i, using fura-2 as an indicator) at 300C. 2. When quiescent uterine muscle strips were stretched at a ramp time of 0 5 s by multiples of 5% of the resting muscle length (Lo) up to 40%, forty-two out of sixty muscle strips responded with a transient active contraction and a [Ca2+]i increase. The minimum excursion of stretch required for contraction was 26 3 + 7 5% of Lo (mean + S.D.). The peak response had an all-or-none property and was almost independent of the duration of stretch. 5. When a stretch of 15-35% of Lo was applied during the relaxation phase of 10 nM oxytocin-induced rhythmic contractions, the first contraction after the stretch occurred earlier than that expected from the control rhythm. However, the frequency of the subsequent rhythm returned to almost the control level even during continued application of stretch, although the half-width of rhythmic contractions was increased during stretch. 6. The present study demonstrates that stretch of uterine muscle induces a transient contraction due to Ca2+ influx, which is myogenic and dependent on the excursion and velocity of stretch. The all-or-none property of the stretch-induced contractions suggests initiation of Ca2+ spikes. Furthermore, stretch modulates the oxytocin-induced rhythmic contractions.

“…Spontaneous uterine contractions depend upon pacemaker depolarization. The ionic mechanisms underlying pacemaker activity have not been fully characterized, but probably involve decreased K+ permeability and increased Na+ or Ca2+ permeability (Parkington & Coleman, 1990). By increasing K+ permeability, hypoxia would tend to reduce the frequency of contractions or abolish them, as is observed.…”

Section: Discussionmentioning

confidence: 99%

Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Heaton

Wray

Eisner

1993

SUMMARY1. We have investigated the role of changes of potassium efflux in the inhibition of uterine force produced by cyanide. K+ efflux (86Rb) was measured from pregnant and non-pregnant rat myometrial strips during metabolic inhibition with cyanide and following manoeuvres to displace intracellular pH (pHi).2. Cyanide greatly reduced or abolished spontaneous contractions. If the membrane was depolarized directly at this stage (by elevating external K+) then contraction redeveloped. This suggests that the initial depression of force is due to a failure of membrane excitation.3. Cyanide reversibly increased 86Rb efflux (30-35%) in both pregnant and nonpregnant uteri and contraction was reduced. The increase in 86Rb efflux with cyanide was not secondary to changes of membrane potential as it also occurred in both high-K+ and Ca2+-free solutions. 6. Intracellular alkalinization produced by the weak base trimethylamine (60 mM) increased the frequency of uterine contraction and the 86Rb efflux. However, there was no effect on the 86Rb efflux in a Ca2+-free solution. The increased efflux is therefore presumably a consequence of the increased frequency.7. It is concluded that metabolic inhibition produced by cyanide, produces an increase in K+ efflux from the myometrium. Part of this efflux is glibenclamide sensitive. This increased K+ efflux will lead to hyperpolarization of the myometrial membrane and thus decrease excitation. Thus reduced surface membrane excitability will contribute to the fall of force in hypoxia; specifically it may cause the initial loss of spontaneous contractions in the uterus.MS 1322