Nifedipine reveals the existence of two discrete components of the progesterone-induced [Ca2+]i transient in human spermatozoa

J. C Kirkman-Brown (Lead / Corresponding author), C. L. R Barratt, S. J Publicover

Research output: Contribution to journalArticle

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Abstract

The steroid progesterone, an agonist of acrosome reaction, induces a biphasic [Ca(2+)](i)-signal in human sperm comprising an initial transient [Ca(2+)](i) elevation, and a subsequent ramp or plateau. Nifedipine, an inhibitor of voltage-operated Ca(2+) channels, inhibits progesterone-induced acrosome reaction in human sperm, but fluorimetric studies have detected no effect of this compound on the progesterone-induced [Ca(2+)](i) signal. We have used single-cell imaging to study the effects of nifedipine on [Ca(2+)](i) signalling in human sperm. Analysis of mean responses from large numbers of cells showed that treatment with nifedipine reduced the duration but not the amplitude of the progesterone-induced [Ca(2+)](i) transient. In control cells, the latency of the transient peak (maximum fluorescence) fell within the range of 30-105 s. In the presence of nifedipine, very few cells peaked "late" (>60 s after application of progesterone). Analysis of transient responses in control cells revealed characteristic "early" and "late" responses, most cells showing both "early" and "late" transients, whereas "late" transients were rare and smaller in the presence of nifedipine. Sustained responses showed strong association with late transients, and occurrence and amplitude of sustained responses were significantly reduced in nifedipine pretreated cells. These findings are consistent with the occurrence of a discrete, nifedipine-sensitive component of the progesterone-induced [Ca(2+)](i) transient that peaks 1-2 min after exposure to the hormone and is crucial for the induction of the sustained [Ca(2+)](i) signal.

Original languageEnglish
Pages (from-to)71-82
Number of pages12
JournalDevelopmental Biology
Volume259
Issue number1
Early online date3 May 2003
DOIs
Publication statusPublished - 1 Jul 2003

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Nifedipine
Progesterone
Spermatozoa
Acrosome Reaction
Architectural Accessibility
Cell Count
Fluorescence
Steroids
Hormones

Keywords

  • Acrosome/drug effects
  • Calcium/metabolism
  • Calcium Channel Blockers/pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Nifedipine/pharmacology
  • Progesterone/pharmacology
  • Spermatozoa/drug effects

Cite this

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abstract = "The steroid progesterone, an agonist of acrosome reaction, induces a biphasic [Ca(2+)](i)-signal in human sperm comprising an initial transient [Ca(2+)](i) elevation, and a subsequent ramp or plateau. Nifedipine, an inhibitor of voltage-operated Ca(2+) channels, inhibits progesterone-induced acrosome reaction in human sperm, but fluorimetric studies have detected no effect of this compound on the progesterone-induced [Ca(2+)](i) signal. We have used single-cell imaging to study the effects of nifedipine on [Ca(2+)](i) signalling in human sperm. Analysis of mean responses from large numbers of cells showed that treatment with nifedipine reduced the duration but not the amplitude of the progesterone-induced [Ca(2+)](i) transient. In control cells, the latency of the transient peak (maximum fluorescence) fell within the range of 30-105 s. In the presence of nifedipine, very few cells peaked {"}late{"} (>60 s after application of progesterone). Analysis of transient responses in control cells revealed characteristic {"}early{"} and {"}late{"} responses, most cells showing both {"}early{"} and {"}late{"} transients, whereas {"}late{"} transients were rare and smaller in the presence of nifedipine. Sustained responses showed strong association with late transients, and occurrence and amplitude of sustained responses were significantly reduced in nifedipine pretreated cells. These findings are consistent with the occurrence of a discrete, nifedipine-sensitive component of the progesterone-induced [Ca(2+)](i) transient that peaks 1-2 min after exposure to the hormone and is crucial for the induction of the sustained [Ca(2+)](i) signal.",
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Nifedipine reveals the existence of two discrete components of the progesterone-induced [Ca2+]i transient in human spermatozoa. / Kirkman-Brown, J. C (Lead / Corresponding author); Barratt, C. L. R; Publicover, S. J.

In: Developmental Biology, Vol. 259, No. 1, 01.07.2003, p. 71-82.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nifedipine reveals the existence of two discrete components of the progesterone-induced [Ca2+]i transient in human spermatozoa

AU - Kirkman-Brown, J. C

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AB - The steroid progesterone, an agonist of acrosome reaction, induces a biphasic [Ca(2+)](i)-signal in human sperm comprising an initial transient [Ca(2+)](i) elevation, and a subsequent ramp or plateau. Nifedipine, an inhibitor of voltage-operated Ca(2+) channels, inhibits progesterone-induced acrosome reaction in human sperm, but fluorimetric studies have detected no effect of this compound on the progesterone-induced [Ca(2+)](i) signal. We have used single-cell imaging to study the effects of nifedipine on [Ca(2+)](i) signalling in human sperm. Analysis of mean responses from large numbers of cells showed that treatment with nifedipine reduced the duration but not the amplitude of the progesterone-induced [Ca(2+)](i) transient. In control cells, the latency of the transient peak (maximum fluorescence) fell within the range of 30-105 s. In the presence of nifedipine, very few cells peaked "late" (>60 s after application of progesterone). Analysis of transient responses in control cells revealed characteristic "early" and "late" responses, most cells showing both "early" and "late" transients, whereas "late" transients were rare and smaller in the presence of nifedipine. Sustained responses showed strong association with late transients, and occurrence and amplitude of sustained responses were significantly reduced in nifedipine pretreated cells. These findings are consistent with the occurrence of a discrete, nifedipine-sensitive component of the progesterone-induced [Ca(2+)](i) transient that peaks 1-2 min after exposure to the hormone and is crucial for the induction of the sustained [Ca(2+)](i) signal.

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KW - Humans

KW - Male

KW - Nifedipine/pharmacology

KW - Progesterone/pharmacology

KW - Spermatozoa/drug effects

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