Neural Regulation of the hear 031109 - Cornell University
Transcript of Neural Regulation of the hear 031109 - Cornell University
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Neural Regulation of the HeartNeural Regulation of the Heart
Jean HardwickIthaca Collegeg
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Preganglionic neuron
Target
Postganglionic neuron
Target
Target
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Autonomic Nervous System
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Sensory innervation
Sensory Inputs• BP• pH• pO2
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Autonomic Innervation of the Heart
Parasympathetic
ACh↓ Heart Rate↓ CACh
NESympathetic
↓ Contractility↓ Cardiac Output
NENE NE↑ Heart Rate↑ Contractility↑ Cardiac Output
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http://www.cvphysiology.com/Arrhythmias/SAN%20action%20potl.gif
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http://www.biosbcc.net/doohan/sample/images/CO%20and%20MAP/0306pace.jpg
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Cardiac Ganglion
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CNS PreganglionicCNS Preganglionic Neurons
SympatheticSympathetic Postganglionic Fibers
ParasympatheticPostganglionic
NeuronsC diCardiac SensoryNeurons
Cardiac Target Cells
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Parasympathetic Cardiac Ganglion
Fast synaptic transmission (excitatory)Fast synaptic transmission (excitatory)ACh (nicotinic receptors)
Other signalsOther signalsACh (muscarinic receptors)NENE NeuropeptidesLocally-generated signalsLocally generated signals
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Parasympathetic Cardiac Ganglion
Preganglionic Fibers
Postganglionic Fibers
Sympathetic P t li iPostganglionicFibers
Sensory Afferents
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Guinea pig cardiac ganglionp g g g
Mawe, et al (1996) Cell Tissue Res 285:281.
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Neurotransmitters
NeuropeptidesNeuropeptidesSensory peptides
Substance P, CGRP,PACAP
PACAP38, PACAP27PACAP 1-27 28-38
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MAP2MAP2Substance P
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CGRP
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PACAP 38MAP2
PACAP 27MAP2
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Physiology
“puffer”containingcontainingtest substance
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Preganglionic fiber
Postganglionic neuronPostganglionic neuron
Phasic Neuron Tonic NeuronPhasic Neuron Tonic Neuron
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Stimulation of fiber inputs
ControlControl
0 Ca++
Wash
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Substance P
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Substance P
Control SP Wash
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PACAP
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Non-traditional Neuromodulators
Immunue mediatorsImmunue mediatorsMast cell activation
HistamineProstaglandins
Nitric Oxide
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Cardiac Mast Cells
Found in high density in mammalian heartFound in high density in mammalian heartStimulated by:
Antigen exposureAntigen exposureSensory neuropeptidesChemoreceptorsChemoreceptors
pH changes, low oxygen
Upon stimulation releaseUpon stimulation, releaseHistamineProstaglandins (synthesized from phospholipids)Prostaglandins (synthesized from phospholipids)
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H HH
H
H
H H
H
H
H
HH
PG’s
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MAP2Histamine
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Parasympathetic Cardiac Ganglion
Preganglionic Fibers
Postganglionic Fibers
Mast cells
Sympathetic P t li iPostganglionicFibers
Sensory Afferents
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Sensitization
Wait
3 weeks
Collect Tissue
Apply OVA totissue to inducemast cell
Inject with OVAth d
3 weeks mast cell degranulation
every other day(3 injections total)
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Mast Cell Degranulation
HYH
H Ovalbumin
HH
HH
H H
AAPGs
PLA2PGs
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Response to Mast Cell Degranulation
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Histamine Responses
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Excitability
) 15
20 Tonic ControlTonic Histamine
z) 15
20 Phasic ControlPhasic Histamine
) 15
20Control, All cellsHistamine, Alll cells #
#
Freq
uenc
y (H
z)
10
15
Freq
uenc
y (H
z
10
15
Freq
uenc
y (H
z)
10
15
##
## #
##
# # ##
#
0 0 0 2 0 4 0 6
AP F
0
5
0 0 0 2 0 4 0 6
AP
0
5
0 0 0 2 0 4 0 6
AP F
0
5 #
##
#
Stimulus (nA)
0.0 0.2 0.4 0.6
Stimulus (nA)
0.0 0.2 0.4 0.6
Stimulus (nA)
0.0 0.2 0.4 0.6
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Nitric Oxide in the Heart
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Nitric Oxide
NOS
NONO
Ca++
NONO
GuanylateCyclasecGMP
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Physiological Actions of NO
Electrophysiological recordings from theElectrophysiological recordings from the cardiac plexus
AChPreganglionic fiber
Intracardiac neuron
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Nitric Oxide
SNP
Control
20 mV
50 msec
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Regulation of neuronal firingPreganglionic fibers
ACh fast depolarization AP generationACh - fast depolarization, AP generationPACAP – slow, long lasting depolarization, increase in excitabilityincrease in excitability
Sensory afferent fibersSP slow depolarization increase in excitabilitySP – slow depolarization, increase in excitability
Mast cellsHistamine depolarization increase in excitabilityHistamine – depolarization, increase in excitability
Intracardiac neuronsNO ti i i EPSP lit dNO – presynaptic increase in EPSP amplitude
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Chronic Heart Disease and Neuronal Regulation
Horackova, M. et al. (2004) Am J Physiol Heart Circ Physiol 287: H1599-H1608
Copyright ©2004 American Physiological Society
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Models of Heart Disease
Myocardial infarctionMyocardial infarctionLigate left ventricular coronary artery6-9 weeks recovery6 9 weeks recovery
Pressure OverloadBand descending dorsal aortaBand descending dorsal aortaProduces left ventricular hypertrophy8-10 weeks recovery8 10 weeks recovery
Sham surgery
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Regulation of NOS levels
Control Chronic MIControl Chronic MInNOSand
MAP2
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Regulation of NOS levels
25
Control
20
Control CMI Sham surgery CPO
##
NO
S c
ells 15
%nN
5
10
0
5
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Mast Cell Density
C t l CMIControl CMI
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Mast Cells
2.0
mm
2 )
1.5
Control MI PO * #
nsity
(cel
ls/m
1.0*
ast C
ell D
en
0.5
M
0.0
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Physiological Changes with Chronic MI
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Physiological Changes with Disease
18
20
ControlH
z) 14
16
18Control with HistaminePO with HistamineMI with Histamine
Freq
uenc
y (
8
10
12
AP
2
4
6
Stimulus Intensity (nA)
0.0 0.2 0.4 0.60
2
y ( )
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Physiological Changes with Diseasey g g
25z)
20ControlControl with PACAPPO with PACAPMI with PACAP
requ
ency
(Hz
10
15
AP F
r
5
10
0.0 0.2 0.4 0.60
Stimulus Intensity (nA)
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PreganglionicInputs
SensoryInputsp Inputs
PACAP
Mast Cells
ACh PACAP
HistamineNO
SPCGRPSensory
Inputs
T t C llTarget Cells
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Acknowledgements
National Institutes of HealthNational Institutes of HealthHeart Lung and Blood Institute
Jeffrey Ardell – ETSUMarie Southerland, DVM – ETSU Rodney Parsons – UVM
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Student CollaboratorsSeth DePuy (’99) Melanie Powers (’01) Beth Peterson (’01) Gina DiMasi (’02) ( ) ( )Kristen Sager (’02) Zach Goldsmith (’02)Greg Jelson (’02) Martha Morin (’03)Bekke Mapes (’03) Brenna Corbett (’03)Bekke Mapes ( 03) Brenna Corbett ( 03)Amy Kotarski (’05) Jay Sellers (’05)Danielle Federico (’05) Abby Wilkes (’06)Andrew Kelley (’05) Megan McManus (’06)Robert Janelli (’07) Nancy Andersen (’07)Ryan Bochacki (’07) Amber Contrastan (’09)y ( ) ( )Caitlin Baran (’09) Lauren Houdek (’10)Noah Mishkin (‘11) Alison Girasole (’11)
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