Neural Regulation of the Heart

Neural Regulation of the Heart
Jean Hardwick
g
Ithaca College
Preganglionic neuron
Postganglionic neuron
Target
Target
Autonomic Nervous System
Sensory innervation
Sensory Inputs
• BP
• pH
• pO2
Autonomic Innervation of the Heart
Parasympathetic
ACh
Sympathetic
NE
ACh
↓ Heart Rate
↓ Contractility
C
↓ Cardiac Output
NE
↑ Heart Rate
↑ Contractility
↑ Cardiac Output
http://www.cvphysiology.com/Arrhythmias/SAN%20action%20potl.gif
http://www.biosbcc.net/doohan/sample/images/CO%20and%20MAP/0306pace.jpg
Cardiac Ganglion
CNS Preganglionic
Neurons
Sympathetic
Postganglionic
Fibers
Cardiac
C
di
Sensory
Neurons
Parasympathetic
Postganglionic
Neurons
Cardiac Target
Cells
Parasympathetic Cardiac Ganglion
„
Fast synaptic transmission (excitatory)
‰
„
ACh (nicotinic receptors)
Other signals
‰
‰
‰
‰
ACh (muscarinic receptors)
NE
Neuropeptides
Locally-generated
Locally
generated signals
Parasympathetic Cardiac Ganglion
Preganglionic Fibers
Postganglionic Fibers
Sympathetic
P t
Postganglionic
li i
Fibers
Sensory Afferents
Guinea p
pigg cardiac ganglion
g g
Mawe, et al (1996) Cell Tissue Res 285:281.
Neurotransmitters
„
Neuropeptides
‰
Sensory peptides
„
‰
Substance P,, CGRP
PACAP
„
PACAP38, PACAP27
PACAP 1-27
28-38
MAP2
Substance P
CGRP
PACAP 38
MAP2
PACAP 27
MAP2
Physiology
“puffer”
containing
test substance
Preganglionic fiber
Postganglionic neuron
Phasic Neuron
Tonic Neuron
Stimulation of fiber inputs
Control
0 Ca++
Wash
Substance P
Substance P
Control
SP
Wash
PACAP
Non-traditional Neuromodulators
„
Immunue mediators
‰
Mast cell activation
„
„
„
Histamine
Prostaglandins
Nitric Oxide
Cardiac Mast Cells
„
„
Found in high density in mammalian heart
Stimulated by:
‰
‰
‰
Antigen exposure
Sensory neuropeptides
Chemoreceptors
„
„
pH changes, low oxygen
Upon stimulation
stimulation, release
‰
‰
Histamine
Prostaglandins (synthesized from phospholipids)
H
H
H
H
H
H
H
H
H
PG’s
MAP2
Histamine
Parasympathetic Cardiac Ganglion
Preganglionic Fibers
Mast cells
Postganglionic Fibers
Sympathetic
P t
Postganglionic
li i
Fibers
Sensory Afferents
Sensitization
Wait
3 weeks
Inject with OVA
every other
th d
day
(3 injections total)
Collect
Tissue
Apply OVA to
tissue to induce
mast cell
degranulation
Mast Cell Degranulation
H
H
H
Ovalbumin
Y
H
H
H
H
H
PGs
PGs
AA
PLA2
Response to Mast Cell Degranulation
Histamine Responses
Excitability
20
20
#
5
#
15
#
10
#
#
#
#
5
#
15
#
#
#
10
5
#
0
0
00
0.0
AP F
Frequency (Hz))
#
AP Frequency (Hz
z)
AP F
Frequency (Hz))
#
#
10
Tonic Control
Tonic Histamine
#
15
#
20
Phasic Control
Phasic Histamine
Control, All cells
Histamine, Alll cells
02
0.2
04
0.4
Stimulus (nA)
06
0.6
0
00
0.0
02
0.2
04
0.4
Stimulus (nA)
06
0.6
00
0.0
02
0.2
04
0.4
Stimulus (nA)
06
0.6
Nitric Oxide in the Heart
Nitric Oxide
NOS
Ca++
NO
cGMP
Guanylate
Cyclase
Physiological Actions of NO
„
Electrophysiological recordings from the
cardiac plexus
ACh
Preganglionic fiber
Intracardiac neuron
Nitric Oxide
SNP
Control
20 mV
50 msec
Regulation of neuronal firing
„
Preganglionic fibers
‰
‰
„
Sensory afferent fibers
‰
„
SP – slow depolarization
depolarization, increase in excitability
Mast cells
‰
„
ACh - fast depolarization,
depolarization AP generation
PACAP – slow, long lasting depolarization,
increase in excitability
Histamine – depolarization,
depolarization increase in excitability
Intracardiac neurons
‰
NO – presynaptic
ti increase
i
in
i EPSP amplitude
lit d
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
Models of Heart Disease
„
Myocardial infarction
‰
‰
„
Pressure Overload
‰
‰
‰
„
Ligate left ventricular coronary artery
6-9
6
9 weeks recovery
Band descending dorsal aorta
Produces left ventricular hypertrophy
8-10
8
10 weeks recovery
Sham surgery
Regulation of NOS levels
Control
Chronic MI
nNOS
and
MAP2
Regulation of NOS levels
25
%nN
NOS cells
20
15
10
5
0
Control
CMI
Sham surgery
CPO
#
#
Mast Cell Density
C t l
Control
CMI
Mast Cells
Mast Cell Den
nsity (cells/m
mm2)
2.0
Control
MI
PO
*
#
1.5
*
1.0
0.5
0.0
Physiological Changes with Chronic MI
Physiological Changes with Disease
20
Control
Control with Histamine
PO with Histamine
MI with Histamine
18
AP Frequency (Hz)
16
14
12
10
8
6
4
2
0
0.0
0.2
0.4
Stimulus Intensityy (nA)
( )
0.6
Physiological
y
g
Changes
g with Disease
25
Control
Control with PACAP
PO with PACAP
MI with PACAP
AP Frrequency (Hzz)
20
15
10
5
0
0.0
0.2
0.4
Stimulus Intensity (nA)
0.6
Preganglionic
Inputs
p
Sensory
Inputs
Mast Cells
ACh
PACAP
Histamine
NO
Sensory
Inputs
SP
CGRP
T
Target
t Cells
C ll
Acknowledgements
„
National Institutes of Health
‰ Heart Lung and Blood Institute
„
Jeffrey Ardell – ETSU
Marie Southerland, DVM – ETSU
Rodney Parsons – UVM
„
„
Student Collaborators
Seth DePuy (’99)
Beth Peterson ((’01))
Kristen Sager (’02)
Greg Jelson (’02)
Bekke Mapes ((’03)
03)
Amy Kotarski (’05)
Danielle Federico (’05)
Andrew Kelley (’05)
Robert Janelli (’07)
Ryan
y Bochacki ((’07))
Caitlin Baran (’09)
Noah Mishkin (‘11)
Melanie Powers (’01)
Gina DiMasi ((’02))
Zach Goldsmith (’02)
Martha Morin (’03)
Brenna Corbett (’03)
( 03)
Jay Sellers (’05)
Abby Wilkes (’06)
Megan McManus (’06)
Nancy Andersen (’07)
Amber Contrastan ((’09))
Lauren Houdek (’10)
Alison Girasole (’11)