Prejunctional and postjunctional actions of heptanol and 18β-glycyrretinic acid in the rodent vas deferens

Faisal Rahman, Rohit Manchanda, Keith L. Brain

Research output: Contribution to journalArticlepeer-review

Abstract

Heptanol and 18β-glycyrrhetinic acid (18βGA) block gap junctions, but have other actions on transmitter release that have not been characterised. This study investigates the prejunctional and postjunctional effects of these compounds in guinea pig and mouse vas deferens using intracellular electrophysiological recording and confocal Ca2+ imaging of sympathetic nerve terminals. In mice, heptanol (2 mM) reversibly decreased the amplitude of purinergic excitatory junction potentials (EJPs; 52 ± 5%, P < 0.05) while having little effect on spontaneous excitatory junction potentials (sEJPs). Heptanol (2 mM) reversibly abolished the nerve terminal Ca2+ transient in 52% of terminals. 18βGA (10 μM) decreased the mean EJP amplitude, and increased input resistance in both mouse (137 ± 17%, P < 0.05) and guinea pig (354 ± 50%, P < 0.001) vas deferens indicating gap junction blockade. Further, 18βGA increased the sEJP frequency significantly in guinea pigs (by 71 ± 25%, P < 0.05) and in 5 out of 6 tissues in mice (19 ± 3%, P < 0.05). Moreover, 18βGA depolarised cells from both mice (11 ± 1%, P < 0.01) and guinea pigs (8 ± 1%, P < 0.005). Therefore, we conclude that heptanol (2 mM) decreases neurotransmitter release (given the decrease in EJP amplitude) by abolishing the nerve terminal action potential in a proportion of nerve terminals. 18βGA (10 μM) effectively blocks the gap junctions, but the increase in sEJP frequency suggests an additional prejunctional effect, which might involve the induction of spontaneous nerve terminal action potentials.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalAutonomic Neuroscience: Basic and Clinical
Volume148
Issue number1-2
DOIs
StatePublished - Jun 15 2009
Externally publishedYes

Keywords

  • 18β-glycyrretinic acid
  • Gap junctions
  • Heptanol
  • Smooth muscle
  • Sympathetic neurotransmission

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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