Calcium channel types

Calcium channel blockers minimally interfere with stimulus-secretion coupling in glands and nerve endings because of differences between calcium channel type and sensitivity in different tissues. Verapamil has been shown to inhibit insulin release in humans, but the dosages required are greater than those used in management of angina. 

Wu LG, Westenbroek RE, Borst JG, Catterall WA, Sakmann B. Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses. J. Neurosci. 1999 19 726-736. 

Umemiya M, Berger AJ. Single-channel properties of four calcium channel types in rat motoneurons. J Neurosci 1995 15(3 Pt 2) 2218-24. 

Turner TJ, Lampe RA, Dunlap K. Characterization of presynaptic calcium channels with omega-conotoxin MVIIC and omega-grammotoxin SIA role for a resistant calcium channel type in neurosecretion. Mol Pharmacol 1995 47(2) 348-53. 

Luebke JI, Dunlap K, Turner TJ. Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus. Neuron 1993 ll(5) 895-902. 

B. Type II and type IV drugs act by blocking beta-adrenergic receptors (type II) or calcium channels (type IV). Their actions are discussed elsewhere (type II, p 131 type IV, p 144). 

Regehr WG, Mintz IM (1994) Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses. Nemon 12 605-613... 

Succinimides. Ethosuximide [77-67-8] C2H22NO2 (41) and the related succinknide, methsuximide [77-41-8] C22H23NO2 (42) are used in absence seizure treatment. Like the other anticonvulsants discussed, the mechanism of action of the succinirnides is unclear. Effects on T-type calcium channels and -ATPase activity have been reported (20). Ethosuximide has significant CNS and gastrointestinal (GI) side effect HabiUties (13). 

Opiates iateract with three principal classes of opioid GPCRs )J.-selective for the endorphiQS,5-selective for enkephalins, and K-selective for dynorphias (51). AU. three receptors have been cloned. Each inhibits adenylate cyclase, can activate potassium channels, and inhibit A/-type calcium channels. The classical opiates, morphine and its antagonists naloxone (144) and naltrexone (145), have moderate selectivity for the. -receptor. Pharmacological evidence suggests that there are two subtypes of the. -receptor and three subtypes each of the 5- and K-receptor. An s-opiate receptor may also exist. 

Patients having high plasma renin activity (PRA) (>8 ng/(mLh)) respond best to an ACE inhibitor or a -adrenoceptor blocker those having low PRA (<1 ng/(mLh)) usually elderly and black, respond best to a calcium channel blocker or a diuretic (184). -Adrenoceptor blockers should not be used in patients who have diabetes, asthma, bradycardia, or peripheral vascular diseases. The thiazide-type diuretics (qv) should be used with caution in patients having diabetes. Likewise, -adrenoceptor blockers should not be combined with verapamil or diltiazem because these dmgs slow the atrioventricular nodal conduction in the heart. Calcium channel blockers are preferred in patients having coronary insufficiency diseases because of the cardioprotective effects of these dmgs. 

The methyl groups adjacent to the pyridine nitrogens can also be modified without changing calcium channel blocking activity. The most significant change involves replacement of methyl by a nitrile group. Hantsch type condensation of the nitrobenzaldehyde 43 with methyl acetoacetate and the vinyl amine 44 from isopropyl 3-cyano-3-ketopropionate leads directly to nilvadipine (45) [13]. 

Calcium channels in the plasma membrane activated after receptor-mediated calcium release from intracellular stores. Diese channels are present in many cellular types and play pivotal roles in a multitude of cell functions. It was recently shown that Orai proteins are the pore-forming subunit of CRAC channels. They are activated by STIM proteins that sense the Ca2+ content of the endoplasmic reticulum. 

Furthermore, PKCe is required for nerve growth factor-induced activation of mitogen-activated protein kinases and neurite outgrowth by ethanol. It is also required for ethanol-induced increases in N-type voltage-gated calcium channels in PC 12 neural cells. 

Protein kinase A (PKA) is a cyclic AMP-dependent protein kinase, a member of a family of protein kinases that are activated by binding of cAMP to their two regulatory subunits, which results in the release of two active catalytic subunits. Targets of PKA include L-type calcium channels (the relevant subunit and site of phosphorylation is still uncertain), phospholam-ban (the regulator of the sarcoplasmic calcium ATPase, SERCA) and key enzymes of glucose and lipid metabolism. 

A large number of diugs interfere with the smooth muscle contraction. These compounds lower blood pressure and are referred to as antihypertensive. In this section, only those coumpounds will be mentioned that have a direct effect on smooth muscle tone. Phenylephrine is an agonist on most smooth muscles and activates ax adrenoceptors. Carbachol is an agonist on some smooth muscles and activates contraction through muscarinic receptors. Blockers of the ax-adrenoceptors such as prazosin and urapidil are competitive inhibitors of the ax-receptor in vascular and bladder smooth muscle. Phenoxybenzamine is an ineversible blocker of ax receptors and phentol-amine blocks ax and a2 receptors. Ca2+ channel blockers such as the dihydropyiidines, phenylalkyla-mines and benzothiazepines lower smooth muscle tone by blocking the L-type calcium channel. 

Voltage-dependent Ca2+ channels are a family of multi-subunit complexes of five proteins responding to membrane depolarisation with channel opening allowing the influx of calcium into a cell. Voltage-dependent calcium channels are subdivided into three subfamilies the HVA DHP-sensitive L-type calcium channels, the HVA DHP-insensitive calcium channels and the LVA T-type calcium channels [2]. 

Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83 117-161... 

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites,... 

Matrila MJ, Aranko K, Seppala T Acute effects of huspirone and alcohol on psychomotor skills. J Clin Psychiatry 43 56-60, 1982 McMahon T, Andersen R, Merten P, et al Protein kinase C epsilon mediates upregu-lation ofN-type calcium channels by ethanol. Mol Pharmacol 37 33-58, 2000 Merry], Reynolds CM, Bailey], et al Prophylactic treatment of alcoholism by lithium carbonate. Lancet 2 481 82, 1976... 

Flubendiamide is an example of a new chemical class of insecticides that have been termed phthalic acid diamides (Nauen 2006, Copping and Duke 2007). They are related to the alkaloid ryanodine, which is extracted from Ryania species. Ryanodine affects muscles by binding to calcium channels of the sarcoplasmic reticulum. Ca + ions act as intracellular messengers, and their flux is modulated by calcium channels of this type. The toxic action of ryanodine and synthetic insecticides related to it is due to the disturbance of calcium flux. 

---