Solute Transport across Membranes:- The Neuronal Na⁺ Channel Is a Voltage-Gated Ion Channel

Sodium ion channels in the plasma membranes of neurons and of myocytes of heart and skeletal muscle sense electrical gradients across the membrane and respond by opening or closing. These voltage-gated ion channels are typically very selective for Na over other monovalent or divalent cations (by factors of 100 or more) and have a very high flux rate (>10⁷ ions/s). Normally (in the resting state) in the closed conformation, Na channels are opened—activated—by a reduction in the transmembrane electrical potential, then they undergo very rapid inactivation. Within milliseconds of the opening, the channel closes and remains inactive for many milliseconds. Activation followed by inactivation of Na channels is the basis for signaling by neurons (see Fig. 12–5).

The essential component of a Na⁺ channel is a single, large polypeptide (1,840 amino acid residues) organized into four domains clustered around a central channel (Fig. 11–50a, b), providing a path for Na through the membrane. The path is made Na-specific by a “pore region” composed of the segments between transmembrane helices 5 and 6 of each domain, which fold into the channel. Helix 4 of each domain has a high density of positively charged residues; this segment is believed to move within the membrane in response to changes in the transmembrane voltage, from the “resting” potential of about 60 mV (inside negative) to about +30 mV. The movement of helix 4 triggers opening of the channel, and this is the basis for voltage gating (Fig. 11–50c).

Inactivation of the channel is thought to occur by a ball-and-chain mechanism. A protein domain on the cytosolic surface of the Na channel, the inactivation gate (the ball), is tethered to the channel by a short segment of the polypeptide (the chain) (Fig. 11–50b). This domain is free to move about when the channel is closed, but when it opens, a site on the inner face of the channel becomes available for the tethered ball to bind, blocking the channel. The length of the tether appears to determine how long an ion channel stays open; the longer the tether, the longer the open period. Inactivation of other ion channels may proceed by a similar mechanism.

FIGURE 11–50 Voltage-gated Na channels of neurons. Sodium channels of different tissues and organisms have a variety of subunits, but only the principal subunit (α) is essential. (a) The α subunit is a large protein with four homologous domains (I to IV), each containing six transmembrane helices (1 to 6). Helix 4 in each domain (blue) is the voltage sensor; helix 6 (orange) is thought to be the activation gate. The segments between helices 5 and 6, the pore region (red), form the selectivity filter, and the segment connecting domains III and IV (green) is the inactivation gate. (b) The four domains are wrapped about a central transmembrane channel lined with polar amino acid residues. The segments linking helices 5 and 6 (red) in each domain come together near the extracellular surface to form the selectivity filter, which is conserved in all Na⁺ channels. The filter gives the channel its ability to discriminate between Na⁺ and other ions of similar size. The inactivation gate (green) closes (dotted lines) soon after the activation gate opens. (c) The voltage-sensing mechanism involves movement of helix 4 (blue) perpendicular to the plane of the mem brane in response to a change in transmembrane potential. As shown at the top, the strong positive charge on helix 4 allows it to be pulled inward in response to the inside-negative membrane potential (V_m). Depolarization lessens this pull, and helix 4 relaxes by moving out ward (bottom). This movement is communicated to the activation gate (orange), inducing conformational changes that open the channel in response to depolarization.

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شعبة فاطمة بنت أسد (عليها السلام): ملتقى الكوثر منصةً لتحقيق وعي أسري مستند للقرآن الكريم

شعبة فاطمة بنت أسد (عليها السلام) تطلق النسخة الثالثة من ملتقى الكوثر

استقبال المشاركات في ملتقى الكوثر الثقافي الثالث إيذانًا بانطلاق برامجه التوعوية

في ذكرى زواج النورين.. شعبة التوجيه النسوي تنظم جلسات ثقافية للزائرات

المزيد

الآخبار الصحية

طريقة مبتكرة للكشف المبكر عن أمراض القلب والشرايين

منظمة الصحة تحذر من خطر إدمان الشباب لأكياس النيكوتين

خبراء يحذرون من عادة شائعة تهدد صحة الملايين

خبير يكشف 5 حقائق طبية صادمة وغير معروفة

المزيد

الآخبار التكنلوجية

الأولى في العالم.. الصين تجري تجربة رائدة في الفضاء باستخدام "جنين اصطناعي"

دراسة حديثة تفند ربط التستوستيرون بالمخاطرة لدى الرجال

ميتا تضيف وضع "المحادثة المخفية" إلى تطبيق "واتساب"

فوبيا المرتفعات ليست من الدماغ.. دراسة تكشف السبب

المزيد

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