manu/mldr-zoomed-100char-total-queries-documents

chunk_id stringlengths 3 9	chunk stringlengths 1 100
72_132	others.
72_133	Epilepsy, chronic pain, and addictive drugs such as cocaine, opioids, cannabinoids, and ethanol all
72_134	affect neuronal excitability and heart rate. GIRK channels have been shown to be involved in
72_135	seizure susceptibility, cocaine addiction, and increased tolerance for pain by opioids,
72_136	cannabinoids, and ethanol. This connection suggests that GIRK channel modulators may be useful
72_137	therapeutic agents in the treatment of these conditions. GIRK channel inhibitors may serve to
72_138	treat addictions to cocaine, opioids, cannabinoids, and ethanol while GIRK channel activators may
72_139	serve to treat withdrawal symptoms.
72_140	Alcohol intoxication
72_141	Alcohol intoxication has been shown to be directly connected to the actions of GIRK channels. GIRK
72_142	channels have a hydrophobic pocket that is capable of binding ethanol, the type of alcohol found in
72_143	alcoholic beverages. When ethanol acts as an agonist, GIRK channels in the brain experience
72_144	prolonged opening. This causes decreased neuronal activity, the result of which manifests as the
72_145	symptoms of alcohol intoxication. The discovery of the hydrophobic pocket capable of binding
72_146	ethanol is significant in the field of clinical pharmacology. Agents that can act as agonists to
72_147	this binding site can be potentially useful in the creation of drugs for the treatment of
72_148	neurological disorders such as epilepsy in which neuronal firing exceeds normal levels.
72_149	Breast cancer
72_150	Studies have shown that a link exists between channels with GIRK1 subunits and the beta-adrenergic
72_151	receptor pathway in breast cancer cells responsible for growth regulation of the cells.
72_152	Approximately 40% of primary human breast cancer tissues have been found to carry the mRNA which
72_153	codes for GIRK1 subunits. Treatment of breast cancer tissue with alcohol has been shown to trigger
72_154	increased growth of the cancer cells. The mechanism of this activity is still a subject of
72_155	research.
72_156	Down syndrome
72_157	Altered cardiac regulation is common in adults diagnosed with Down syndrome and may be related to G
72_158	protein-gated ion channels. The KCNJ6 gene is located on chromosome 21 and encodes for the GIRK2
72_159	protein subunit of G protein-gated K+ channels. People with Down Syndrome have three copies of
72_160	chromosome 21, resulting in an overexpression of the GIRK2 subunit. Studies have found that
72_161	recombinant mice overexpressing GIRK2 subunits show altered responses to drugs that activate G
72_162	protein-gated K+ channels. These altered responses were limited to the sino-atrial node and atria,
72_163	both areas which contain many G protein-gated K+ channels. Such findings could potentially lead to
72_164	the development of drugs that can help regulate the cardiac sympathetic-parasympathetic imbalance
72_165	in Down Syndrome adults.
72_166	Chronic atrial fibrillation
72_167	Atrial fibrillation (abnormal heart rhythm) is associated with shorter action potential duration
72_168	and believed to be affected by the G protein-gated K+ channel, IK,ACh. The IK,ACh channel, when
72_169	activated by G proteins, allows for the flow of K+ across the plasma membrane and out of the cell.
72_170	This current hyperpolarizes the cell, thus terminating the action potential. It has been shown that
72_171	in chronic atrial fibrillation there an increase in this inwardly rectifying current because of
72_172	constantly activated IK,ACh channels. Increase in the current results in shorter action potential
72_173	duration experienced in chronic atrial fibrillation and leads to the subsequent fibrillating of the
72_174	cardiac muscle. Blocking IK,ACh channel activity could be a therapeutic target in atrial
72_175	fibrillation and is an area under study.
72_176	Pain management
72_177	GIRK channels have been demonstrated in vivo to be involved in opioid- and ethanol-induced
72_178	analgesia. These specific channels have been the target of recent studies dealing with genetic
72_179	variance and sensitivity to opioid analgesics due to their role in opioid-induced analgesia.
72_180	Several studies have shown that when opioids are prescribed to treat chronic pain, GIRK channels
72_181	are activated by certain GPCRs, namely opioid receptors, which leads to the inhibition of
72_182	nociceptive transmission, thus functioning in pain relief. Furthermore, studies have shown that G
72_183	proteins, specifically the Gi alpha subunit, directly activate GIRKs which were found to
72_184	participate in propagation of morphine-induced analgesia in inflamed spines of mice. Research
72_185	pertaining to chronic pain management continues to be performed in this field.
72_186	See also G protein G protein-coupled receptor Metabotropic receptor References
72_187	Ion channels Electrophysiology Integral membrane proteins
73_0	The Irish Rovers is a group of Irish musicians that originated in Toronto, Canada. Formed in 1963
73_1	named after the traditional song "The Irish Rover" they are best known for their international
73_2	television series, contributing to the popularisation of Irish Music in North America, and for the
73_3	songs "The Unicorn", "Drunken Sailor", "Wasn't That a Party", "The Orange and the Green", "Whiskey
73_4	on a Sunday", "Lily the Pink" and "The Black Velvet Band".
73_5	The primary voices heard in the group's early songs were Will Millar (tenor), Jimmy Ferguson
73_6	(baritone), George Millar and Joe Millar, and in the last twenty years, also John Reynolds and Ian
73_7	Millar. Wilcil McDowell's accordion has been a signature sound of the band throughout their more
73_8	than fifty years.
73_9	Founding member George Millar and his cousin Ian are both from Ballymena, Davey Walker from Armagh,
73_10	Sean O'Driscoll from Cork, Gerry O'Connor from Dundalk, with Morris Crum from Carnlough and
73_11	percussionist Fred Graham from Belfast. Flute and whistle player Geoffrey Kelly was born in
73_12	Dumfries, Scotland.
73_13	In the 1980s, the group briefly renamed itself The Rovers. During this period, their "Wasn't That a
73_14	Party" led to crossover success in the country rock genre.
73_15	The Irish Rovers have represented Canada at five World Expos, and in 2018 were honoured as one of
73_16	Ireland's greatest exports at Dublin, Ireland's EPIC The Irish Emigration Museum.
73_17	History
73_18	Northern Ireland
73_19	The brothers George Millar and Will Millar were both born in Ballymena, County Antrim, Northern
73_20	Ireland. The children grew up in a musical household as their father Bob played button-key
73_21	accordion for several bands throughout the years. Their cousin Joe Millar, who also sang, took part
73_22	in the family kitchen parties playing button-key accordion and harmonica. As children, George and
73_23	Will performed with their sister, Sandra Beech as "The Millar Kids" in Ireland, before the family
73_24	emigrated to Canada.
73_25	Early years
73_26	In 1963, George met fellow Irish native Jimmy Ferguson at an Irish function in Toronto. They sang
73_27	together until dawn, and founded the Irish Rovers. According to a Calgary Herald article in 1971,
73_28	"George and Jimmy formed the first Irish Rovers for an amateur variety show in Toronto and won."
73_29	George's cousin, Joe also soon emigrated to Toronto and was recruited as he stepped off the plane.
73_30	The name "The Irish Rovers" was suggested by George's mother. The traditional Irish song about a
73_31	sailing ship had been a favourite from their kitchen parties in Ballymena. For a short time,
73_32	George, Jimmy and Joe were joined by Vic Marcus and Doug Henderson. George's father, Bob, became
73_33	The Irish Rovers's first manager booking the new band at folk song festivals, clubs, hootenannies
73_34	and The Port o' Call. According to a 1964 newspaper in the Millars' home town in Ireland, "The folk
73_35	singing 'boom' in the United States and Canada proved profitable for three young Ballymena men who
73_36	form the nucleus of a popular, Toronto-based group who call themselves 'The Irish Rovers.'”
73_37	In the early 60s, Will Millar and his friend Brian Evans performed in a Toronto Calypso group, The
73_38	Kalypso Kews. After moving to Calgary, Will formed a folk trio in Calgary along with another Ulster
73_39	native, Derek Swinson. He also developed quite a following singing at Phil's Pancake House, and
73_40	then landing a job singing on Calgary's Just 4 Fun, a local TV show for children.
73_41	In 1964, after more than six months performing in the Toronto area, George and Jimmy left to visit
73_42	Will in Calgary. In 1979, Jimmy told Canadian Music Magazine, "We actually formed the group in
73_43	Toronto. I sang, George played guitar and at that time Joe was playing a little button key

72_132

others.

72_133

Epilepsy, chronic pain, and addictive drugs such as cocaine, opioids, cannabinoids, and ethanol all

72_134

affect neuronal excitability and heart rate. GIRK channels have been shown to be involved in

72_135

seizure susceptibility, cocaine addiction, and increased tolerance for pain by opioids,

72_136

cannabinoids, and ethanol. This connection suggests that GIRK channel modulators may be useful

72_137

therapeutic agents in the treatment of these conditions. GIRK channel inhibitors may serve to

72_138

treat addictions to cocaine, opioids, cannabinoids, and ethanol while GIRK channel activators may

72_139

serve to treat withdrawal symptoms.

72_140

Alcohol intoxication

72_141

Alcohol intoxication has been shown to be directly connected to the actions of GIRK channels. GIRK

72_142

channels have a hydrophobic pocket that is capable of binding ethanol, the type of alcohol found in

72_143

alcoholic beverages. When ethanol acts as an agonist, GIRK channels in the brain experience

72_144

prolonged opening. This causes decreased neuronal activity, the result of which manifests as the

72_145

symptoms of alcohol intoxication. The discovery of the hydrophobic pocket capable of binding

72_146

ethanol is significant in the field of clinical pharmacology. Agents that can act as agonists to

72_147

this binding site can be potentially useful in the creation of drugs for the treatment of

72_148

neurological disorders such as epilepsy in which neuronal firing exceeds normal levels.

72_149

Breast cancer

72_150

Studies have shown that a link exists between channels with GIRK1 subunits and the beta-adrenergic

72_151

receptor pathway in breast cancer cells responsible for growth regulation of the cells.

72_152

Approximately 40% of primary human breast cancer tissues have been found to carry the mRNA which

72_153

codes for GIRK1 subunits. Treatment of breast cancer tissue with alcohol has been shown to trigger

72_154

increased growth of the cancer cells. The mechanism of this activity is still a subject of

72_155

research.

72_156

Down syndrome

72_157

Altered cardiac regulation is common in adults diagnosed with Down syndrome and may be related to G

72_158

protein-gated ion channels. The KCNJ6 gene is located on chromosome 21 and encodes for the GIRK2

72_159

protein subunit of G protein-gated K+ channels. People with Down Syndrome have three copies of

72_160

chromosome 21, resulting in an overexpression of the GIRK2 subunit. Studies have found that

72_161

recombinant mice overexpressing GIRK2 subunits show altered responses to drugs that activate G

72_162

protein-gated K+ channels. These altered responses were limited to the sino-atrial node and atria,

72_163

both areas which contain many G protein-gated K+ channels. Such findings could potentially lead to

72_164

the development of drugs that can help regulate the cardiac sympathetic-parasympathetic imbalance

72_165

in Down Syndrome adults.

72_166

Chronic atrial fibrillation

72_167

Atrial fibrillation (abnormal heart rhythm) is associated with shorter action potential duration

72_168

and believed to be affected by the G protein-gated K+ channel, IK,ACh. The IK,ACh channel, when

72_169

activated by G proteins, allows for the flow of K+ across the plasma membrane and out of the cell.

72_170

This current hyperpolarizes the cell, thus terminating the action potential. It has been shown that

72_171

in chronic atrial fibrillation there an increase in this inwardly rectifying current because of

72_172

constantly activated IK,ACh channels. Increase in the current results in shorter action potential

72_173

duration experienced in chronic atrial fibrillation and leads to the subsequent fibrillating of the

72_174

cardiac muscle. Blocking IK,ACh channel activity could be a therapeutic target in atrial

72_175

fibrillation and is an area under study.

72_176

Pain management

72_177

GIRK channels have been demonstrated in vivo to be involved in opioid- and ethanol-induced

72_178

analgesia. These specific channels have been the target of recent studies dealing with genetic

72_179

variance and sensitivity to opioid analgesics due to their role in opioid-induced analgesia.

72_180

Several studies have shown that when opioids are prescribed to treat chronic pain, GIRK channels

72_181

are activated by certain GPCRs, namely opioid receptors, which leads to the inhibition of

72_182

nociceptive transmission, thus functioning in pain relief. Furthermore, studies have shown that G

72_183

proteins, specifically the Gi alpha subunit, directly activate GIRKs which were found to

72_184

participate in propagation of morphine-induced analgesia in inflamed spines of mice. Research

72_185

pertaining to chronic pain management continues to be performed in this field.

72_186

See also G protein G protein-coupled receptor Metabotropic receptor References

72_187

Ion channels Electrophysiology Integral membrane proteins

73_0

The Irish Rovers is a group of Irish musicians that originated in Toronto, Canada. Formed in 1963

73_1

named after the traditional song "The Irish Rover" they are best known for their international

73_2

television series, contributing to the popularisation of Irish Music in North America, and for the

73_3

songs "The Unicorn", "Drunken Sailor", "Wasn't That a Party", "The Orange and the Green", "Whiskey

73_4

on a Sunday", "Lily the Pink" and "The Black Velvet Band".

73_5

The primary voices heard in the group's early songs were Will Millar (tenor), Jimmy Ferguson

73_6

(baritone), George Millar and Joe Millar, and in the last twenty years, also John Reynolds and Ian

73_7

Millar. Wilcil McDowell's accordion has been a signature sound of the band throughout their more

73_8

than fifty years.

73_9

Founding member George Millar and his cousin Ian are both from Ballymena, Davey Walker from Armagh,

73_10

Sean O'Driscoll from Cork, Gerry O'Connor from Dundalk, with Morris Crum from Carnlough and

73_11

percussionist Fred Graham from Belfast. Flute and whistle player Geoffrey Kelly was born in

73_12

Dumfries, Scotland.

73_13

In the 1980s, the group briefly renamed itself The Rovers. During this period, their "Wasn't That a

73_14

Party" led to crossover success in the country rock genre.

73_15

The Irish Rovers have represented Canada at five World Expos, and in 2018 were honoured as one of

73_16

Ireland's greatest exports at Dublin, Ireland's EPIC The Irish Emigration Museum.

73_17

History

73_18

Northern Ireland

73_19

The brothers George Millar and Will Millar were both born in Ballymena, County Antrim, Northern

73_20

Ireland. The children grew up in a musical household as their father Bob played button-key

73_21

accordion for several bands throughout the years. Their cousin Joe Millar, who also sang, took part

73_22

in the family kitchen parties playing button-key accordion and harmonica. As children, George and

73_23

Will performed with their sister, Sandra Beech as "The Millar Kids" in Ireland, before the family

73_24

emigrated to Canada.

73_25

Early years

73_26

In 1963, George met fellow Irish native Jimmy Ferguson at an Irish function in Toronto. They sang

73_27

together until dawn, and founded the Irish Rovers. According to a Calgary Herald article in 1971,

73_28

"George and Jimmy formed the first Irish Rovers for an amateur variety show in Toronto and won."

73_29

George's cousin, Joe also soon emigrated to Toronto and was recruited as he stepped off the plane.

73_30

The name "The Irish Rovers" was suggested by George's mother. The traditional Irish song about a

73_31

sailing ship had been a favourite from their kitchen parties in Ballymena. For a short time,

73_32

George, Jimmy and Joe were joined by Vic Marcus and Doug Henderson. George's father, Bob, became

73_33

The Irish Rovers's first manager booking the new band at folk song festivals, clubs, hootenannies

73_34

and The Port o' Call. According to a 1964 newspaper in the Millars' home town in Ireland, "The folk

73_35

singing 'boom' in the United States and Canada proved profitable for three young Ballymena men who

73_36

form the nucleus of a popular, Toronto-based group who call themselves 'The Irish Rovers.'”

73_37

In the early 60s, Will Millar and his friend Brian Evans performed in a Toronto Calypso group, The

73_38

Kalypso Kews. After moving to Calgary, Will formed a folk trio in Calgary along with another Ulster

73_39

native, Derek Swinson. He also developed quite a following singing at Phil's Pancake House, and

73_40

then landing a job singing on Calgary's Just 4 Fun, a local TV show for children.

73_41

In 1964, after more than six months performing in the Toronto area, George and Jimmy left to visit

73_42

Will in Calgary. In 1979, Jimmy told Canadian Music Magazine, "We actually formed the group in

73_43

Toronto. I sang, George played guitar and at that time Joe was playing a little button key