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Vagal tone determines the relative temperature dependency of heart rate in vertebrates
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Abstracts / Comparative Biochemistry and Physiology, Part A 146 (2007) S165–S170
density is almost ubiquitous response in fish cardiac myocytes, which partially compensates for direct temperature effects on AP duration. doi:10.1016/j.cbpa.2007.01.350
A11.9 Acute temperature changes may affect the role of the Na+/Ca2+-exchanger in trout cardiomyocytes R. Birkedal, H. Shiels, (The University of Manchester) In rainbow trout heart, an increase in temperature often results in a decrease in contractile force. This is related to a decrease in the amplitude of the Ca2+-transient, [Ca2+]i, in cardiomyocytes. Although Ca2+-influx via L-type Ca2+channels decreases in a temperature-dependent manner, this alone cannot account for the temperature-dependent changes in [Ca2+]i. Thus, other Ca2+ pathways such as Ca2+-release from the sarcoplasmic reticulum and/or reverse-mode Na+/ Ca2+-exchange, NCX, must be involved. We measured the intracellular Na+-concentration in rainbow trout cardiomyocytes and found that it is very high (∼ 13 mM) compared to most mammals. This will favour Ca2+-influx via reversemode NCX during excitation–contraction coupling, and we hypothesize that reverse-mode NCX contributes to the Ca2+transient. Interestingly, calculations using our recent data and previously published data suggest that the Ca2+-influx via reverse-mode NCX decreases with an increase in temperature. Therefore, we propose that the temperature-dependent decrease in [Ca2+]i is explained by a decrease in Ca2+influx via both L-type Ca2+-channels and reverse-mode NCX. doi:10.1016/j.cbpa.2007.01.351
A11.10 Control of turtle (Trachemys scripta) cardiac activity during anoxia: III. Electrophysiological modification of ventricular tissue J. Stecyk, A. Farrell, (University of British Columbia); V. Paajanen, M. Vornanen, (University of Joensuu) Cardiac activity of the freshwater turtle (Trachemys scripta) is greatly depressed with cold acclimation and anoxia. We examined what electrophysiological modifications accompany and perhaps facilitate this depression of cardiac activity. Turtles were first acclimated to 21 °C or 5 °C and held under either normoxic or anoxic (6 h at 21 °C; 14 days at 5 °C) conditions. Then, we measured ventricular action potentials (APs) using spontaneously contracting whole-heart preparations and whole-cell current densities of
sarcolemmal ion channels using isolated ventricular myocytes under appropriate normoxic and anoxic conditions. Compared with 21 °C-acclimated turtles, 5 °C-acclimated turtles exhibited a less negative resting membrane potential (by 29 mV), a 4.7-fold slower AP upstroke rate and a 4.2fold greater AP duration (APD). Correspondingly, peak density of ventricular voltage-gated Na+ (INa) and L-type Ca2+ currents and inward slope conductance of inward rectifier K+ (IK1) channel current were approximately 1/7th, 1/13th, and half that of 21 °C-acclimated ventricular myocytes, respectively. With anoxia at 21 °C, peak INa density doubled and ventricular APD increased by 47%; a change proportional to the reported ∼ 30% reduction of intrinsic heart rate. In contrast, with anoxia at 5 °C, ventricular AP characteristics were unaffected, and of the ion currents investigated, only the inward conductance via IK1 changed significantly (reduced by 46%). We conclude that cold acclimation, more so than prolonged anoxia, results in substantial modifications of ventricular APs and reduction of ion current densities. These acclimatory changes likely prepare the turtle ventricle for the ordeal of winter anoxic conditions. Supported by NSERC Canada and the Academy of Finland. doi:10.1016/j.cbpa.2007.01.352
A11.11 Vagal tone determines the relative temperature dependency of heart rate in vertebrates T. Taylor, H. Campbell, S. Egginton, (The University of Birmingham); N. Skovgaard, (Aarhus University) Most vertebrates exhibit an inhibitory vagal tonus on the heart that predominates over excitatory sympathetic tone. Thus, overall heart rate and its beat-to-beat modulation, including respiration-related variations, is determined by phasic depolarisation of the intrinsic pacemaker, governed by efferent activity in the cardiac vagus. In a wide range of species the extent of cardiac vagal tone has been shown to vary with temperature. In the dogfish, Scyliorhinus release of vagal tone, either by denervation or injection of atropine, resulted in increases in heart rate which varied with temperature. Similar data were obtained for the eel, Anguilla, where adaptation to temperature change was largely mediated by the vagus. In Xenopus heart rate following atropinisation increased by 10 beats/min at 5 °C and by 55 beats/min at 25 °C. In Rana, allowed 18 h to recover from anaesthesia, although vagal tone on the heart was slight it did increase with temperature. Antarctic fishes, which live at temperatures between − 2 and +2 °C, have very low heart rates, attributable to uniquely high levels of vagal tone. This is further evidence for the predominant role of the vagus in determining the relationships between temperature and heart rate. Recent data have
Abstracts / Comparative Biochemistry and Physiology, Part A 146 (2007) S165–S170
indicated that this control is of central importance in determining seasonal changes in metabolic rate. doi:10.1016/j.cbpa.2007.01.353
A11.12 Seasonal acclimation in cardiac activity: Mammals vs. fish S. Egginton, D. Hauton, H. Campbell, S. May, S. Young, (University of Birmingham) The dominance of vagal tonus over cardiac sympathetic tone is accentuated on acute cold exposure of mammals to a core temperature of 25 °C, leading to a bradycardia appropriate for the reduction in metabolic rate. When investigated by Power Spectral Analysis, changes in heart rate variability (HRV) can be seen as a decrease in the ratio of low frequency to high frequency (LF:HF) power in rats. In hamsters this only occurs after a period of cold acclimation to an environmental temperature of 4 °C, whilst maintaining core temperature. Interestingly, despite ∼ 30% cardiac hypertrophy on chronic cold exposure, the power output of acclimated hamster hearts (either rate-pressure product, or dP/dt) is less than those from euthermic controls, although less temperature-sensitive. Acclimation of common carp to similar environmental temperatures leads to a commensurate drop in core temperature, with a similar degree of cardiac hypertrophy. In this case, heart rate varied directly with oxygen consumption, although HR decreased and HRV increased in a non-linear manner between 25 and 5 °C on chronic exposure. Interestingly, acute changes in temperature resulted in a decrease in vagal tone on warming, but no significant change on cooling. Pharmacological blockade shows both chronic and acute responses to be dominated by cholinergic influences, with little role for adrenergic control. Supported by NERC. doi:10.1016/j.cbpa.2007.01.354
A11.13 Cold-induced cardiac hypertrophy does not preserve cardiac performance D. Hauton, S. Egginton, (University of Birmingham) Cold acclimation of Golden hamsters led to cardiac hypertrophy. Acute cold (25 °C) exposure of unpaced Langendorffperfused hearts led to a decrease in heart rate (P < 0.001) and for control hearts led to a significant decrease in systolic pressure (P < 0.01). Cold acclimation to 4 °C was without affect on heart rate for hearts perfused at either 25 °C or 37 °C. However, cold acclimation led to a preservation of systolic pressures following acute cold exposure, whereas control hearts showed a significant decrease in systolic pressure (P < 0.01). For both control and cold-adapted hearts diastolic function was preserved when perfused at both 25 °C and 37 °C. Estimation of peak dP/
S169
dt for cold-acclimated hearts revealed that cold-induced hypertrophy led to a 75% reduction in dP/dt at both 25 °C (P < 0.01) and 37 °C (P < 0.01) when compared with control hearts. Corresponding significant changes were also noted for rate-pressure product estimations. Interestingly, for cold acclimated hearts peak dP/dt and rate-pressure product was achieved at double the ventricle volume recorded for control hearts. Acute hypothermia led to a ∼66% decrease in coronary flow for perfused control hearts, however, for cold-acclimated hearts coronary flow was preserved under hypothermic conditions. These data indicate that cold acclimation of the hibernator heart may result in the preservation of developed pressures by the heart under hypothermic conditions, although these hearts show poor contractile performance when compared to control hearts. This may have implications for the transition from hibernation to arousal. doi:10.1016/j.cbpa.2007.01.355
A11.14 Temperature acclimation modifies sinatrial pacemaker mechanism of the trout heart J. Haverinen, M. Vornanen, (University of Joensuu) Acclimation to cold increases basal heart rate in rainbow trout (Oncorhynchus mykiss). This study tests the hypothesis that thermal acclimation modifies pacemaker mechanism of the trout heart. To this end, action potentials (AP) were recorded in intact sinoatrial tissue and enzymatically isolated pacemaker cells of trout acclimated at 4 °C (cold-acclimated, c.a.) or 18 °C (warmacclimated, w.a.). With electrophysiological recordings the primary pacemaker was located at the base of the sinoatrial valve, and histological examination indicated a morphologically distinct ring of nodal tissue in this location. Intrinsic rate (APs/ min) of the pacemaker was higher in c.a. (46 ± 6) than w.a. (38 ± 3) (p < 0.05) trout at 11 °C, and a similar difference was found in isolated pacemaker cells (44 ± 6 vs. 38 ± 6) (p < 0.05). Inhibition of sarcoplasmic reticulum (SR) with 10 μM ryanodine and 1 μM thapsigargin did not effect heart rate in either w.a. or c.a. trout. Half-maximal blockade of the delayed rectifier potassium current (IKr) with 0.1 μM E-4031 reduced heart rate more in w.a. (from 45 ± 1 to 24 ± 5) than c.a. trout (from 56 ± 3 to 48 ± 2) (p < 0.05). These findings indicate that thermal acclimation modifies pacemaker mechanism of the trout heart, and suggest that coldinduced increase in heart rate is at least partly due to high density of the IKr in the c.a. trout, while contribution of SR Ca2+ release to thermal compensation of heart rate is negligible. doi:10.1016/j.cbpa.2007.01.356
A11.15 Increased PRPC expression in human carotid artery lesions P. Ethirajan, (Manchester Metropolitan University)
Abstracts / Comparative Biochemistry and Physiology, Part A 146 (2007) S165–S170
density is almost ubiquitous response in fish cardiac myocytes, which partially compensates for direct temperature effects on AP duration. doi:10.1016/j.cbpa.2007.01.350
A11.9 Acute temperature changes may affect the role of the Na+/Ca2+-exchanger in trout cardiomyocytes R. Birkedal, H. Shiels, (The University of Manchester) In rainbow trout heart, an increase in temperature often results in a decrease in contractile force. This is related to a decrease in the amplitude of the Ca2+-transient, [Ca2+]i, in cardiomyocytes. Although Ca2+-influx via L-type Ca2+channels decreases in a temperature-dependent manner, this alone cannot account for the temperature-dependent changes in [Ca2+]i. Thus, other Ca2+ pathways such as Ca2+-release from the sarcoplasmic reticulum and/or reverse-mode Na+/ Ca2+-exchange, NCX, must be involved. We measured the intracellular Na+-concentration in rainbow trout cardiomyocytes and found that it is very high (∼ 13 mM) compared to most mammals. This will favour Ca2+-influx via reversemode NCX during excitation–contraction coupling, and we hypothesize that reverse-mode NCX contributes to the Ca2+transient. Interestingly, calculations using our recent data and previously published data suggest that the Ca2+-influx via reverse-mode NCX decreases with an increase in temperature. Therefore, we propose that the temperature-dependent decrease in [Ca2+]i is explained by a decrease in Ca2+influx via both L-type Ca2+-channels and reverse-mode NCX. doi:10.1016/j.cbpa.2007.01.351
A11.10 Control of turtle (Trachemys scripta) cardiac activity during anoxia: III. Electrophysiological modification of ventricular tissue J. Stecyk, A. Farrell, (University of British Columbia); V. Paajanen, M. Vornanen, (University of Joensuu) Cardiac activity of the freshwater turtle (Trachemys scripta) is greatly depressed with cold acclimation and anoxia. We examined what electrophysiological modifications accompany and perhaps facilitate this depression of cardiac activity. Turtles were first acclimated to 21 °C or 5 °C and held under either normoxic or anoxic (6 h at 21 °C; 14 days at 5 °C) conditions. Then, we measured ventricular action potentials (APs) using spontaneously contracting whole-heart preparations and whole-cell current densities of
sarcolemmal ion channels using isolated ventricular myocytes under appropriate normoxic and anoxic conditions. Compared with 21 °C-acclimated turtles, 5 °C-acclimated turtles exhibited a less negative resting membrane potential (by 29 mV), a 4.7-fold slower AP upstroke rate and a 4.2fold greater AP duration (APD). Correspondingly, peak density of ventricular voltage-gated Na+ (INa) and L-type Ca2+ currents and inward slope conductance of inward rectifier K+ (IK1) channel current were approximately 1/7th, 1/13th, and half that of 21 °C-acclimated ventricular myocytes, respectively. With anoxia at 21 °C, peak INa density doubled and ventricular APD increased by 47%; a change proportional to the reported ∼ 30% reduction of intrinsic heart rate. In contrast, with anoxia at 5 °C, ventricular AP characteristics were unaffected, and of the ion currents investigated, only the inward conductance via IK1 changed significantly (reduced by 46%). We conclude that cold acclimation, more so than prolonged anoxia, results in substantial modifications of ventricular APs and reduction of ion current densities. These acclimatory changes likely prepare the turtle ventricle for the ordeal of winter anoxic conditions. Supported by NSERC Canada and the Academy of Finland. doi:10.1016/j.cbpa.2007.01.352
A11.11 Vagal tone determines the relative temperature dependency of heart rate in vertebrates T. Taylor, H. Campbell, S. Egginton, (The University of Birmingham); N. Skovgaard, (Aarhus University) Most vertebrates exhibit an inhibitory vagal tonus on the heart that predominates over excitatory sympathetic tone. Thus, overall heart rate and its beat-to-beat modulation, including respiration-related variations, is determined by phasic depolarisation of the intrinsic pacemaker, governed by efferent activity in the cardiac vagus. In a wide range of species the extent of cardiac vagal tone has been shown to vary with temperature. In the dogfish, Scyliorhinus release of vagal tone, either by denervation or injection of atropine, resulted in increases in heart rate which varied with temperature. Similar data were obtained for the eel, Anguilla, where adaptation to temperature change was largely mediated by the vagus. In Xenopus heart rate following atropinisation increased by 10 beats/min at 5 °C and by 55 beats/min at 25 °C. In Rana, allowed 18 h to recover from anaesthesia, although vagal tone on the heart was slight it did increase with temperature. Antarctic fishes, which live at temperatures between − 2 and +2 °C, have very low heart rates, attributable to uniquely high levels of vagal tone. This is further evidence for the predominant role of the vagus in determining the relationships between temperature and heart rate. Recent data have
Abstracts / Comparative Biochemistry and Physiology, Part A 146 (2007) S165–S170
indicated that this control is of central importance in determining seasonal changes in metabolic rate. doi:10.1016/j.cbpa.2007.01.353
A11.12 Seasonal acclimation in cardiac activity: Mammals vs. fish S. Egginton, D. Hauton, H. Campbell, S. May, S. Young, (University of Birmingham) The dominance of vagal tonus over cardiac sympathetic tone is accentuated on acute cold exposure of mammals to a core temperature of 25 °C, leading to a bradycardia appropriate for the reduction in metabolic rate. When investigated by Power Spectral Analysis, changes in heart rate variability (HRV) can be seen as a decrease in the ratio of low frequency to high frequency (LF:HF) power in rats. In hamsters this only occurs after a period of cold acclimation to an environmental temperature of 4 °C, whilst maintaining core temperature. Interestingly, despite ∼ 30% cardiac hypertrophy on chronic cold exposure, the power output of acclimated hamster hearts (either rate-pressure product, or dP/dt) is less than those from euthermic controls, although less temperature-sensitive. Acclimation of common carp to similar environmental temperatures leads to a commensurate drop in core temperature, with a similar degree of cardiac hypertrophy. In this case, heart rate varied directly with oxygen consumption, although HR decreased and HRV increased in a non-linear manner between 25 and 5 °C on chronic exposure. Interestingly, acute changes in temperature resulted in a decrease in vagal tone on warming, but no significant change on cooling. Pharmacological blockade shows both chronic and acute responses to be dominated by cholinergic influences, with little role for adrenergic control. Supported by NERC. doi:10.1016/j.cbpa.2007.01.354
A11.13 Cold-induced cardiac hypertrophy does not preserve cardiac performance D. Hauton, S. Egginton, (University of Birmingham) Cold acclimation of Golden hamsters led to cardiac hypertrophy. Acute cold (25 °C) exposure of unpaced Langendorffperfused hearts led to a decrease in heart rate (P < 0.001) and for control hearts led to a significant decrease in systolic pressure (P < 0.01). Cold acclimation to 4 °C was without affect on heart rate for hearts perfused at either 25 °C or 37 °C. However, cold acclimation led to a preservation of systolic pressures following acute cold exposure, whereas control hearts showed a significant decrease in systolic pressure (P < 0.01). For both control and cold-adapted hearts diastolic function was preserved when perfused at both 25 °C and 37 °C. Estimation of peak dP/
S169
dt for cold-acclimated hearts revealed that cold-induced hypertrophy led to a 75% reduction in dP/dt at both 25 °C (P < 0.01) and 37 °C (P < 0.01) when compared with control hearts. Corresponding significant changes were also noted for rate-pressure product estimations. Interestingly, for cold acclimated hearts peak dP/dt and rate-pressure product was achieved at double the ventricle volume recorded for control hearts. Acute hypothermia led to a ∼66% decrease in coronary flow for perfused control hearts, however, for cold-acclimated hearts coronary flow was preserved under hypothermic conditions. These data indicate that cold acclimation of the hibernator heart may result in the preservation of developed pressures by the heart under hypothermic conditions, although these hearts show poor contractile performance when compared to control hearts. This may have implications for the transition from hibernation to arousal. doi:10.1016/j.cbpa.2007.01.355
A11.14 Temperature acclimation modifies sinatrial pacemaker mechanism of the trout heart J. Haverinen, M. Vornanen, (University of Joensuu) Acclimation to cold increases basal heart rate in rainbow trout (Oncorhynchus mykiss). This study tests the hypothesis that thermal acclimation modifies pacemaker mechanism of the trout heart. To this end, action potentials (AP) were recorded in intact sinoatrial tissue and enzymatically isolated pacemaker cells of trout acclimated at 4 °C (cold-acclimated, c.a.) or 18 °C (warmacclimated, w.a.). With electrophysiological recordings the primary pacemaker was located at the base of the sinoatrial valve, and histological examination indicated a morphologically distinct ring of nodal tissue in this location. Intrinsic rate (APs/ min) of the pacemaker was higher in c.a. (46 ± 6) than w.a. (38 ± 3) (p < 0.05) trout at 11 °C, and a similar difference was found in isolated pacemaker cells (44 ± 6 vs. 38 ± 6) (p < 0.05). Inhibition of sarcoplasmic reticulum (SR) with 10 μM ryanodine and 1 μM thapsigargin did not effect heart rate in either w.a. or c.a. trout. Half-maximal blockade of the delayed rectifier potassium current (IKr) with 0.1 μM E-4031 reduced heart rate more in w.a. (from 45 ± 1 to 24 ± 5) than c.a. trout (from 56 ± 3 to 48 ± 2) (p < 0.05). These findings indicate that thermal acclimation modifies pacemaker mechanism of the trout heart, and suggest that coldinduced increase in heart rate is at least partly due to high density of the IKr in the c.a. trout, while contribution of SR Ca2+ release to thermal compensation of heart rate is negligible. doi:10.1016/j.cbpa.2007.01.356
A11.15 Increased PRPC expression in human carotid artery lesions P. Ethirajan, (Manchester Metropolitan University)