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Dr. Gerard Sergeant

Position: Lecturer
Email: info@icbc.ie

Research Interests

Dr. Gerard Sergeant My main research focus is centred around the cellular mechanisms responsible for pacemaker activity in interstitial cells of Cajal (ICC). These cells were once thought to be uniquely expressed in the gastro-intestinal tract however studies from our lab and others have now reported their expression in range of smooth muscles including the vasculature and the upper and lower urinary tract. We primarily focus on ICC in the urethra. There is now growing evidence that these cells act as electrical pacemakers in the urethra which regulate myogenic tone (Sergeant et al., 2000). Isolated ICC are spontaneously active, developing spontaneous inward currents under voltage clamp and depolarisations in current clamp mode. These events were found to be due to activation of Ca2+ activated Cl- channels by regularly occuring Ca2+ waves (Johnston et al., 2005). The mechanisms responsible for generation of Ca2+ waves in ICC are complex, relying not only on Ca2+ release from intracellular stores via IP3 and ryanodine sensitive channels (Sergeant et al.,, 2001) but also on Ca2+ influx across the plasma membrane, mostly likely via reverse mode Na+ / Ca2+ exchange (Bradley et al., 2006). A recent study also found that this activity is regulated by Ca2+ uptake into mitochondria (et al., 2008) and current studies are aimed at elucidating how these mechanisms interact.

Pacemaker activity in urethral ICC is also regulated by inhibitory and excitatory neurotransmitters. For example the frequency of pacemaker activity is increased by noradrenaline and slowed by nitric oxide (Sergeant et al., 2002 & 2006) respectively. ATP is also known to be an important neurotransmitter in the urethra and studies in our lab are currently investigating the mechanisms underlying ATP regulation of urethral tone.

Publications

  • 2008 G. P. Sergeant, M. Craven, M. A. Hollywood, N. G. McHale and K. D. Thornbury. Spontaneous Ca2+ waves in isolated myocytes from rabbit corpus cavernosum: modulation by the NO/cGMP pathway. J. Sex Med. 2009 Apr;6(4):958-66.
  • 2008 Gerard P Sergeant, Keith D Thornbury, Noel G McHale and Mark A Hollywood, Role of mitochondria in modulation of spontaneous Ca2+ waves in freshly dispersed ICC from the rabbit urethra. Journal of Physiology, 586 (Pt 19): 4631-4642
  • 2006 GP Sergeant, MA Hollywood. KD Thornbury & NG McHale. Calcium signalling in urethral ICC. J Physiol. 2006 Nov 1;576(Pt 3):715-20
  • 2006 McHale NG, Hollywood MA, Sergeant GP, Shafei M, Thornbury KT, Ward SM. Organization and function of ICC in the lower urinary tract J Physiol. 2006 Nov 1;576(Pt 3):689-94
  • 2006 Shuk Yin M Yeung, Susumu Ohya, Gerard P Sergeant, Vladimír Pucovsky & Iain A Greenwood. Pharmacological and molecular characterisation of ultra-fast activating K+ currents in murine portal vein myocytes. Br J Pharmacol. 2006 Nov;149(6):676-86.
  • 2006 Sergeant GP, Thornbury KD, McHale NG, Hollywood MA. Interstitial cells of Cajal in the urethra. J Cell Mol Med. 2006 Apr-Jun;10(2):280-91.
  • 2006 Bradley E, Hollywood MA, Johnston L, Large RJ, Matsuda T, Baba A, McHale NG, Thornbury KD, Sergeant GP. Contribution of reverse Na+-Ca2+ exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra. J Physiol 1;574(Pt 3):651-61.
  • 2006 Sergeant GP, Johnston L, McHale NG, Thornbury KD, Hollywood MA. Activation of the cGMP/PKG pathway inhibits electrical activity in rabbit urethral interstitial cells of Cajal by reducing the spatial spread of Ca2+ waves. J Physiol. 2006 1;574(Pt 1):167-81
  • 2006 McHale N, Hollywood M, Sergeant G, Thornbury K. Origin of Spontaneous Rhythmicity in Smooth Muscle. J Physiol 1;570 (Pt1):23-8.
  • 2005 Bradley E, Hollywood MA, McHale NG, Thornbury KD, Sergeant GP. Pacemaker activity in urethral interstitial cells is not dependent on capacitative calcium entry. Am J Physiol Cell Physiol. 289(3):C625-632.
  • 2005 L.M. Johnston, Gerard P. Sergeant, M.A. Hollywood, K.D. Thornbury and N.G. McHale. Calcium oscillations in interstitial cells of the rabbit urethra (J Physiol 1;565(Pt 2):449-61).
  • 2005 Gerard P Sergeant, Gregory C. Amberg, Susumu Ohya, James A. Reihill, Brian A. Perrino, Yuji Imaizumi, Burton Horowitz, Kenton M. Sanders and Sang Don Koh. Regulation of Kv4.3 current by Ca2+-calmodulin-dependent protein kinase II. Am J Physiol (Cell Physiology) 2005 Feb;288(2):C304-13
  • 2004 Michael Craven, Gerard P Sergeant, Mark A Hollywood, Noel G McHale, and Keith D Thornbury. Modulation of spontaneous Ca2+-activated Cl- currents in the rabbit corpus cavernosum by the NO/cGMP pathway. J Physiol. 2004 Apr 15;556(Pt 2):495-506
  • 2003 Ohya S, Sergeant GP, Greenwood IA, Horowitz B. Molecular variants of KCNQ channels are expressed in murine portal vein myocytes: A role in delayed rectifier current. Circ Res. 2003 May 16;92(9):1016-23.
  • 2003 Hollywood MA, Sergeant GP, McHale NG, Thornbury KD. Activation of Ca2+ -activated Cl- current by depolarizing steps in rabbit urethral interstitial cells. Am J Physiol Cell Physiol. 2003 Aug;285(2):C327-33
  • 2002 Walker RL, Koh SD, Sergeant GP, Sanders KM, Horowitz B. TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal. American Journal of Physiology (Cell Physiology). Dec; 283(6):C1637-C1645.
  • 2002 Sergeant GP, Large RJ, Beckett EA, McGeough CM, Ward SM, Horowitz B. Microarray comparison of normal and W/Wv mice in the gastric fundus indicates a supersensitive phenotype. Physiological Genomics. Oct 2; 11(1):1-9.
  • 2002 Sergeant GP, Thornbury KD, McHale NG, Hollywood MA. Characterization of norepinephrine-evoked inward currents in interstitial cells isolated from the rabbit urethra. American Journal of Physiology (Cell Physiology). Sep; 283(3):C885-94.
  • 2001 Koh SD, Monaghan K, Sergeant GP, Ro S, Walker RL, Sanders KM, Horowitz B. TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. An essential role in smooth muscle inhibitory neurotransmission. Journal of Biological Chemistry. Nov 23; 276(47):44338-46.
  • 2001 Sergeant GP, Hollywood MA, McHale NG, Thornbury KD. Spontaneous Ca2+ activated Cl- currents in isolated urethral smooth muscle cells. Journal of Urology. Sep; 166(3):1161-6.
  • 2001 Sergeant GP, Hollywood MA, McCloskey KD, McHale NG, Thornbury KD. Role of IP(3) in modulation of spontaneous activity in pacemaker cells of rabbit urethra. American Journal of Physiology (Cell Physiology). May; 280(5):C1349-56.
  • 2000 Sergeant GP, Hollywood MA, McCloskey KD, Thornbury KD, McHale NG. Specialized pacemaking cells in the rabbit urethra. Journal of Physiology. Jul 15; 526 Pt 2:359-66.

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