Conway Review Lecture 1998
23/06/1998 in University College Cork
Tonic and Phasic Activity in Smooth Muscle
Dr. Keith D. Thornbury, Smooth Muscle Group, The Queen’s University of Belfast, 97, Lisburn Road, Belfast BT9 7BL, Northern Ireland
Firstly, I would like to thank the Council of the Biological Sciences section of the Royal Academy of Medicine in Ireland for awarding me the privilege of giving the 1998 Conway Review Lecture. Edward J. Conway FRS, was such an awe-inspiring figure in Irish Science that it is with a great deal of humility that I embark upon a lecture in his memory. Conway himself was noted to have been quite a shy man, but was reported to be at his conversational .best when he had a glass of whiskey in his hand. Indeed, one friend recalled how Conway ‘entertained the Irish delegates in his hotel room in Brussels after the Biochemical Congress in 1955 and he had those fellows from Queen’s singing “Johnsons’ Motor Car” and “The Wearing of the Green” and other such rebel songs before the night was out’.
Well, as a fellow from Queen’s, I’m afraid that even in these times of peace and reconciliation, my singing voice is so poor that I will have to decline request for a repeat performance – purely on humanitarian grounds, you understand!
The lecture will revolve around the discussion of two very different smooth muscle preparations, mesenteric lymphatic ducts and proximal urethra. Each of these tissues generates a different pattern of spontaneous contraction adapted to fulfil their contrasting functions. While lymphatics are designed as a smooth muscle pump that propels the lymph, the urethra spends most of the time in a state of contracture to maintain urinary continence, but every so often must relax suddenly to permit micturition.
We have studied the electrical and mechanical behaviour of two very different smooth muscle preparations, mesenteric lymphatic ducts and proximal urethra. These tissues generate different patterns of spontaneous contraction adapted to fulfil their contrasting functions. While lymphatics undergo regular phasic contractions and relaxations, suited to their role in propelling lymph, the urethra remains in a state of contracture to maintain urinary continence. The challenge is to understand how both of these achieve their respective roles.
Interestingly, electrical activity of lymphatics resembles that in the heart in having a one to one relationship between the action potential and phasic contraction. Patch clamp studies have shown that lymphatic cells express 3 ionic currents that are not present in urethral cells, but are shared with cardiac muscle. These are, i) fast Na + current, ii) T-type Ca 2§ current and iii) a hyperpolarisation-activated cation current, If. The fast Na § current is ideally suited to the propagation of the action potential over large distances, as required by a vessel capable of generating a rapid well co-ordinated contraction along its length. The T-current and If, on the other hand, appear to be involved in electrical pacemaking as they are in the heart.
The urethra does not usually undergo regular phasic contractions and it lacks these currents. Instead, urethral tone may depend on an interaction between L-type Ca z+ current and a large Ca2+-activated CI” current. Activation of CI” channels (perhaps by spontaneous release O f Ca 2+ from intracellular stores) would depolarise the membrane potential to within the ‘window current’ range for L-type Ca z§ channels and result in Ca 2+ influx and contraction. This process may be maintained for a time by positive feedback whereby the influx of Ca z§ continues to activate the Ci” channels.