title: The cellular basis for enhanced volume-modulated cardiac output in fish hearts.
abstract: During vertebrate evolution there has been a shift in the way in which the heart varies cardiac output (the product of heart rate and stroke volume). While mammals, birds, and amphibians increase cardiac output through large increases in heart rate and only modest increases (approximately 30%) in stroke volume, fish and some reptiles use modest increases in heart rate and very large increases in stroke volume (up to 300%). The cellular mechanisms underlying these fundamentally different approaches to cardiac output modulation are unknown. We hypothesized that the divergence between volume modulation and frequency modulation lies in the response of different vertebrate myocardium to stretch. We tested this by progressively stretching individual cardiac myocytes from the fish heart while measuring sarcomere length (SL), developed tension, and intracellular Ca2+ ([Ca2+]i) transients. We show that in fish cardiac myocytes, active tension increases at SLs greater than those previously demonstrated for intact mammalian myocytes, representing a twofold increase in the functional ascending limb of the length-tension relationship. The mechanism of action is a length-dependent increase in myofilament Ca2+ sensitivity, rather than changes in the [Ca2+]i transient or actin filament length in the fish cell. The capacity for greater sarcomere extension in fish myocardium may be linked to the low resting tension that is developed during stretch. These adaptations allow the fish heart to volume modulate and thus underpin the fundamental difference between the way fish and higher vertebrates vary cardiac output.
authors.affiliation: Institute of Membrane and Systems Biology, University of Leeds, UK. holly.shiels@manchester.ac.uk
authors.forename: Holly A
authors.initials: HA
authors.lastname: Shiels
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Calaghan
authors.forename: Ed
authors.initials: E
authors.lastname: White
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D017686:Oncorhynchus mykiss / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology
chemical_list: D002118:Calcium