Calcium ion channels

Systemic and coronary arteries are influenced by movement of calcium across cell membranes of vascular smooth muscle. The contractions of cardiac and vascular smooth muscle depend on movement of extracellular calcium ions into these walls through specific ion channels. Calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem), nicardipine (Cardene), nifedipine (Procardia), and verapamil (Calan), inhibit die movement of calcium ions across cell membranes. This results in less calcium available for the transmission of nerve impulses (Fig. 41-1). This drug action of the calcium channel blockers (also known as slow channel blockers) has several effects on die heart, including an effect on die smooth muscle of arteries and arterioles. These drug dilate coronary arteries and arterioles, which in turn deliver more oxygen to cardiac muscle. Dilation of peripheral arteries reduces die workload of die heart. The end effect of these drug is the same as that of die nitrates. 

Catterall WA et al Compendium of voltage-gated ion channels Calcium channels. Pharmacol Rev 2003 55 579. [PMID 14657414]... 

Ion channels Calcium (type N), calcium (type T and L), chloride, potassium (low conduct). 

A subset of ion channels not gated by traditional neurotransmitters represents another receptor class. These iaclude potassium, calcium, sodium, and cychc adenosiae monophosphate (cAMP)-gated channels (14—16) for which a large number of synthetic molecules exist that alter ceUular function. 

Verapamil (Table 1), the first slow channel calcium blocker synthesized to selectively inhibit the transmembrane influx of calcium ions into cells, lowers blood pressure in hypertensive patients having good organ perfusion particularly with increased renal blood flow. Sustained-release verapamil for once a day dosing is available for the treatment of hypertension. Constipation is a prominent side effect. Headache, dizziness, and edema are frequent and verapamil can sometimes cause AV conduction disturbances and AV block. Verapamil should not be used in combination with -adrenoceptor blockers because of the synergistic negative effects on heart rate and contractile force. 

The resting membrane potential of most excitable cells is around —60 to —80 mV. This gradient is maintained by the activity of various ion channels. When the potassium channels of the cell open, potassium efflux occurs and hyperpolari2ation results. This decreases calcium channel openings, which ia turn preveats the influx of calcium iato the cell lea ding to a decrease ia iatraceUular calcium ia the smooth muscles of the vasculature. The vascular smooth muscles thea relax and the systemic blood pressure faUs. 

Some metals, such as cadmium, cobalt, and lead, are selectively car-diotoxic. They depress contractivity and slow down conduction in the cardiac-system. They may also cause morphological alterations, e.g., cobalt, which was once used to prevent excessive foam formation in beers, caused cardiomyopathy among heavy beer drinkers. Some of the metals also block ion channels in myocytes. Manganese and nickel block calcium channels, whereas barium is a strong inducer of cardiac arrhythmia. 

Epithelial calcium channel 1 (ECaCl), synonym TRJPV5, is a member ofthe TRP family of ion channels, implicated in vitamin D-dependent transcellular Ca2+ transport in epithelial cells ofthe kidney, placenta and the intestine. 

Besides sodium channels, other ion channels such calcium- and potassium channels as well as certain ligand-gated channels are affected by local anaesthetics. However, this plays only a minor role for nerve block but may have more impact on adverse effects induced by systemical concentrations of these drags. 

Stimulation of mAChRs also results in the activation or inhibition of a large number of ion channels [5]. For example, stimulation of Mi receptors leads to the suppression of the so-called M current, a voltage-dependent Recurrent found in various neuronal tissues. M2 receptors, on the other hand, mediate the opening of cardiac Ikcacii) channels, and both M2 and M4 receptors are linked to the inhibition of voltage-sensitive calcium channels [5]. 

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,... 

The ion channel receptors are relatively simple in functional terms because the primary response to receptor activation is generated by the ion channel which is an integral part of the protein. Therefore, no accessory proteins are needed to observe the response to nicotinic AChR activation and the full functioning of the receptor can be observed by isolating and purifying the protein biochemically and reconstituting the protein in an artificial lipid membrane. In contrast, the G-protein-coupled receptors require both G-proteins and those elements such as phospholipase-C illustrated in Fig. 3.1, in order to observe the response to receptor activation (in this case a rise in intracellular calcium concentration resulting from the action of IP3 on intracellular calcium stores). 

T-type calcium channel Maybridge (55 K) and ion channel inhibitor db (8 K), Catalyst search 3 hits of 25 tested [123]... 

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