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ORIGINAL RESEARCH—BASIC SCIENCE: Voltage-dependent Ca2+ Currents Contribute to Spontaneous Ca2+ Waves in Rabbit Corpus Cavernosum Myocytes

Authors


Keith Thornbury, MB, PhD, Smooth Muscle Research Centre, Dundalk Institute of Technology, Dublin Road, Dundalk, Co Louth, N/A, Ireland. Tel: +00353429370526; Fax: +00353429370509; E-mail: keith.thornbury@dkit.ie

ABSTRACT

Introduction.  Corpus cavernosum myocytes generate spontaneous tone that contributes to penile detumescence. It is essential to elucidate how tone is generated to fully understand the processes involved in erection. Tissue experiments have shown that blockers of voltage-dependent Ca2+ channels (VDCCs) reduce tone. However, there is also a widespread belief that these channels are poorly expressed in this tissue. Furthermore, it is unclear how VDCC would interact with recently described intracellular Ca2+ waves, which initiate contractions.

Aims.  (i) To directly examine VDCC currents in freshly isolated corpus cavernosum myocytes; and (ii) to study the relationship between VDCC and intracellular Ca2+ waves.

Main Outcome Measures.  VDCC and cytosolic Ca2+ were measured using patch clamp and confocal microscopy.

Methods.  Male New Zealand white rabbits were euthanized and corpus cavernosum myocytes dispersed enzymatically for patch clamp recording and confocal Ca2+ imaging (using fluo-4AM).

Results.  Isolated myocytes developed robust VDCC that could be separated into two components. One activated at −45 mV, reversed at +40 mV, inactivated with a V1/2 of −27 mV and was enhanced by Ba2+. This component was blocked with nifedipine, but not Ni2+ or mibefradil. The other component inactivated with a V1/2 of −87 mV, was unchanged in Ba2+, and was blocked by Ni2+ or mibefradil, but not nifedipine. Even though Ni2+ had no effect on intracellular Ca2+ waves, nifedipine blocked them, although localized Ca2+ events remained.

Conclusions.  At least two VDCC are expressed in rabbit corpus cavernousum myocytes. One may be designated L-type Ca2+ current, whereas the other is a putative T-type current. The L-current facilitates conversion of local Ca2+ events into global Ca2+ waves, whereas the putative T-current plays little part in this process. These results provide a new basis for understanding the role of L-type Ca2+ current in generating detumescent tone in the corpus cavernosum. McCloskey C, Cagney V, Large R, Hollywood M, Sergeant G, McHale N, and Thornbury K. Voltage-dependent Ca2+ currents contribute to spontaneous Ca2+ waves in rabbit corpus cavernosum myocytes. J Sex Med 2009;6:3019–3031.

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