iberiotoxin
| style="float: right; clear: right; margin: 0 0 0.5em 1em; background: #ffffff;" class="toccolours" border="0" cellpadding="1" align="right" width="280" |
| bgcolor="#eeeeee" |Pyr - Phe - Thr - Asp - Val - Asp - Cys - Ser - Val - Ser - Lys - Glu - Cys - Trp - Ser - Val - Cys - Lys - Asp - Leu - Phe - Gly - Val - Asp - Arg - Gly - Lys - Cys - Met - Gly - Lys - Lys - Cys - Arg - Cys - Tyr - Gln - OH |
| bgcolor="#e7dcc3" |Disulfide bridges: Cys7 - Cys28, Cys13 - Cys33, Cys17 - Cys35 |
Iberiotoxin (IbTX) is an ion channel toxin purified from the Eastern Indian red scorpion Hottentotta tamulus.
Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels.
Chemistry
Iberiotoxin is a 37-amino acid peptide. The formula is C179H274N50O55S7.{{cite journal | last1 = Ferrat | first1 = G | last2 = Bernard | first2 = C | last3 = Fremont | first3 = V | last4 = Mullmann | first4 = TJ | last5 = Giangiacomo | first5 = KM | last6 = Darbon | first6 = H | title = Structural basis for alpha-K toxin specificity for K+ channels revealed through the solution 1H NMR structures of two noxiustoxin-iberiotoxin chimeras | journal = Biochemistry | volume = 40 | issue = 37 | pages = 10998–1006 | year = 2001 | pmid = 11551195 | doi=10.1021/bi010228e}} It is also known as "Potassium channel toxin alpha-KTx 1.3" or IbTx. The complete amino acid sequence has been defined and it displays 68% sequence homology with charybdotoxin.{{cite journal | last1 = Galvez | first1 = A | last2 = Gimenez-Gallego | first2 = G | last3 = Reuben | first3 = JP | last4 = Roy-Contancin | first4 = L | last5 = Feigenbaum | first5 = P | last6 = Kaczorowski | first6 = GJ | last7 = Garcia | first7 = ML | title = Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Hottentotta tamulus | journal = The Journal of Biological Chemistry | volume = 265 | issue = 19 | pages = 11083–90 | year = 1990 | doi = 10.1016/S0021-9258(19)38560-6 | pmid = 1694175 | doi-access = free | hdl = 10261/177752 | hdl-access = free }}
Target and mode of action
Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels (maxiK or BK channels) with high affinity (Kd ~1 nM).{{cite journal | last1 = Candia | first1 = S | last2 = Garcia | first2 = ML | last3 = Latorre | first3 = R | title = Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)-activated K+ channel | journal = Biophysical Journal | volume = 63 | issue = 2 | pages = 583–90 | year = 1992 | pmid = 1384740 | pmc = 1262182 | doi = 10.1016/S0006-3495(92)81630-2 | bibcode=1992BpJ....63..583C}} It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.
Toxicity
The venom produces mainly cardiopulmonary abnormalities like circulatory derangements, myocarditis and changes in cardiac sarcolemmal ATPase and by these abnormalities it can finally cause death. In rural India the scorpion and its venom is a commonly known factor of children's death. The venom initially causes transient cholinergic stimulation (vomiting, profuse sweating, bradycardia, priapism, hypersalivation, and hypotension) which is followed by sustained adrenergic hyperactivity (hypertension, tachycardia, and myocardial failure). The adrenergic phase but not the cholinergic phase is a dose-dependent phenomenon.{{cite journal | last1 = Bawaskar | first1 = HS | last2 = Bawaskar | first2 = PH | title = Management of the cardiovascular manifestations of poisoning by the Indian red scorpion (Hottentotta tamulus) | journal = British Heart Journal | volume = 68 | issue = 5 | pages = 478–80 | year = 1992 | pmid = 1467032 | pmc = 1025191 | doi=10.1136/hrt.68.11.478}}
Treatment
Treatment is mainly symptomatic. Local pain is treated by injecting dehydroemetine at the site of the sting. Hypovolaemia is corrected by oral rehydration solution. Agitated, confused and non-cooperative patients are given a 5% dextrose saline drip. Patients with hypertension on admission are given a single dose of 5 mg sublingual nifedipine and oral prazosin. The blood pressure in patients with hypertension is controlled with sublingual nifedipine alone. Patients with pulmonary oedema are propped up and given intravenous aminophylline, intravenous sodium bicarbonate, oral prazosin, and oxygen by mask.